The endomembrane system allows transportation of proteins, lipids, and polysaccharides within eukaryotic cells. It includes the endoplasmic reticulum, Golgi apparatus, endosomes, lysosomes, and vacuoles. Transport vesicles carry cargo between compartments along cytoskeletal networks. Protein processing occurs as proteins move from the rough ER to Golgi, gaining modifications. The Golgi complexes further modifies proteins and sorts them for secretion or transport to other organelles. Vesicle coats aid in transport specificity. SNARE proteins mediate membrane fusion between transport vesicles and their target compartments.
1. Membrane trafficking allows the transfer of cargo between organelles through transport vesicles that form and fuse with target membranes.
2. Transport vesicles are coated with protein complexes that help generate the vesicles and select cargo for transport. Vesicles move cargo between organelles like the ER, Golgi apparatus, and endosomes.
3. Rab GTPases and SNARE proteins ensure vesicles dock and fuse with the correct target membrane, delivering cargo to its destination compartment.
Organelles interact to carry out important cellular processes like material uptake/release, protein synthesis, and digestion.
(1) Endocytosis and exocytosis allow cells to take in and release material through vesicle trafficking between the plasma membrane and endosomes/lysosomes. (2) The ER and Golgi apparatus work together to synthesize, modify, and transport proteins, with the ER producing proteins and the Golgi processing and packaging them. (3) Lysosomes digest material through phagocytosis, autophagy, and other pathways, while the proteasome degrades unwanted cytosolic proteins. Defects in these organelle interactions can cause diseases.
The document discusses protein sorting in Golgi bodies. It describes how proteins are modified and sorted as they pass through the cis, medial, and trans faces of the Golgi apparatus. Proteins undergo processing like glycosylation and are targeted to their final destinations, such as organelles, vesicles, or secretion. The Golgi apparatus plays a key role in modifying and sorting proteins to their correct locations within and outside the cell.
Günter Blobel and Bernhard Dobberstein provided experimental evidence supporting the signal hypothesis proposed earlier by Blobel and Sabatini. Through in vitro translation experiments using membrane-bound ribosomes from murine myeloma cells, they showed that immunoglobulin light chains containing an amino-terminal signal sequence were incorporated into the microsomal membranes and had the signal cleaved, while light chains lacking a signal sequence were not incorporated. This provided strong evidence that a signal sequence on the nascent polypeptide targets it for attachment to the membrane during translation.
Golgi apparatus ppt (introduction structure and Function)Dryogeshcsv
The Golgi apparatus is a membrane-bound organelle found in eukaryotic cells that packages and modifies proteins and lipids. It consists of stacked, flattened sacs called cisternae. Proteins enter the Golgi at the cis face and undergo processing and modification as they move through the cisternae towards the trans face. At the trans face, proteins are selectively packaged into vesicles and transported to their final destinations within or outside the cell. The Golgi apparatus plays important roles in protein modification, secretion, and sorting of macromolecules.
The document discusses the Golgi apparatus, which packages and modifies proteins and lipids within eukaryotic cells. It describes the Golgi apparatus as consisting of stacked sacs called cisternae with a cis-facing side that receives vesicles from the ER and a trans-facing side that exports vesicles. The Golgi apparatus modifies proteins through phosphorylation, sulfation, and glycosylation as they move between cisternae, and then sorts proteins into vesicles for transport to other parts of the cell through either the constitutive or regulated secretory pathways.
golgi apparatus structure and function.pptxInamUlHaqKhan6
The Golgi apparatus is a membrane-bound organelle found in eukaryotic cells that packages and modifies proteins and lipids. It consists of stacked, flattened sacs called cisternae. Molecules enter the Golgi through the cis face and undergo processing and modification as they move through the cisternae towards the trans face. At the trans face, molecules are packaged into vesicles and transported throughout the cell. The Golgi apparatus plays key roles in protein modification, secretion, and sorting of molecules to their final destinations in the cell.
The document discusses the endomembrane system, including the endoplasmic reticulum (ER) and Golgi complex. The ER is divided into rough ER, where proteins are synthesized, and smooth ER, which functions in lipid and steroid synthesis. Newly synthesized proteins are modified in the Golgi complex through glycosylation as they progress through cis, medial, and trans cisternae. The trans Golgi network sorts proteins to their final destinations, such as secretion or lysosomes.
1. Membrane trafficking allows the transfer of cargo between organelles through transport vesicles that form and fuse with target membranes.
2. Transport vesicles are coated with protein complexes that help generate the vesicles and select cargo for transport. Vesicles move cargo between organelles like the ER, Golgi apparatus, and endosomes.
3. Rab GTPases and SNARE proteins ensure vesicles dock and fuse with the correct target membrane, delivering cargo to its destination compartment.
Organelles interact to carry out important cellular processes like material uptake/release, protein synthesis, and digestion.
(1) Endocytosis and exocytosis allow cells to take in and release material through vesicle trafficking between the plasma membrane and endosomes/lysosomes. (2) The ER and Golgi apparatus work together to synthesize, modify, and transport proteins, with the ER producing proteins and the Golgi processing and packaging them. (3) Lysosomes digest material through phagocytosis, autophagy, and other pathways, while the proteasome degrades unwanted cytosolic proteins. Defects in these organelle interactions can cause diseases.
The document discusses protein sorting in Golgi bodies. It describes how proteins are modified and sorted as they pass through the cis, medial, and trans faces of the Golgi apparatus. Proteins undergo processing like glycosylation and are targeted to their final destinations, such as organelles, vesicles, or secretion. The Golgi apparatus plays a key role in modifying and sorting proteins to their correct locations within and outside the cell.
Günter Blobel and Bernhard Dobberstein provided experimental evidence supporting the signal hypothesis proposed earlier by Blobel and Sabatini. Through in vitro translation experiments using membrane-bound ribosomes from murine myeloma cells, they showed that immunoglobulin light chains containing an amino-terminal signal sequence were incorporated into the microsomal membranes and had the signal cleaved, while light chains lacking a signal sequence were not incorporated. This provided strong evidence that a signal sequence on the nascent polypeptide targets it for attachment to the membrane during translation.
Golgi apparatus ppt (introduction structure and Function)Dryogeshcsv
The Golgi apparatus is a membrane-bound organelle found in eukaryotic cells that packages and modifies proteins and lipids. It consists of stacked, flattened sacs called cisternae. Proteins enter the Golgi at the cis face and undergo processing and modification as they move through the cisternae towards the trans face. At the trans face, proteins are selectively packaged into vesicles and transported to their final destinations within or outside the cell. The Golgi apparatus plays important roles in protein modification, secretion, and sorting of macromolecules.
The document discusses the Golgi apparatus, which packages and modifies proteins and lipids within eukaryotic cells. It describes the Golgi apparatus as consisting of stacked sacs called cisternae with a cis-facing side that receives vesicles from the ER and a trans-facing side that exports vesicles. The Golgi apparatus modifies proteins through phosphorylation, sulfation, and glycosylation as they move between cisternae, and then sorts proteins into vesicles for transport to other parts of the cell through either the constitutive or regulated secretory pathways.
golgi apparatus structure and function.pptxInamUlHaqKhan6
The Golgi apparatus is a membrane-bound organelle found in eukaryotic cells that packages and modifies proteins and lipids. It consists of stacked, flattened sacs called cisternae. Molecules enter the Golgi through the cis face and undergo processing and modification as they move through the cisternae towards the trans face. At the trans face, molecules are packaged into vesicles and transported throughout the cell. The Golgi apparatus plays key roles in protein modification, secretion, and sorting of molecules to their final destinations in the cell.
The document discusses the endomembrane system, including the endoplasmic reticulum (ER) and Golgi complex. The ER is divided into rough ER, where proteins are synthesized, and smooth ER, which functions in lipid and steroid synthesis. Newly synthesized proteins are modified in the Golgi complex through glycosylation as they progress through cis, medial, and trans cisternae. The trans Golgi network sorts proteins to their final destinations, such as secretion or lysosomes.
The endomembrane system includes organelles like the nuclear envelope, endoplasmic reticulum, Golgi apparatus, lysosomes, vesicles, and plasma membrane. It works to modify, package, and transport lipids and proteins. The endoplasmic reticulum consists of rough and smooth regions that synthesize proteins and lipids. The Golgi apparatus further modifies and sorts proteins and lipids before they are transported to other organelles or released from the cell. Together, these membrane-bound organelles work cooperatively to process materials within eukaryotic cells.
The document discusses various pathways of protein trafficking in cells. It describes how proteins are targeted to different organelles like the endoplasmic reticulum, Golgi apparatus, mitochondria, chloroplasts, peroxisomes, and lysosomes. Proteins can be targeted co-translationally as they are synthesized or post-translationally after completion. The ER and Golgi play important roles in modifying proteins through folding, glycosylation and sorting before they are packaged into vesicles and transported to their final destinations. Defects in these trafficking pathways can lead to human diseases.
Structure and function of endoplasmic reticulum and golgi.pptxdivya1313
The document summarizes the structure and functions of the endoplasmic reticulum and Golgi bodies. It describes the ER as a network of membrane-enclosed channels involved in protein synthesis and processing. The Golgi body modifies and sorts proteins and lipids from the ER for transport within the cell or export. Vesicles transport proteins between organelles like the ER, Golgi body, and lysosomes for modification, sorting, and final destination.
1. Eukaryotic cells transport materials between membrane-bound organelles using vesicles that bud from donor membranes and fuse with acceptor membranes.
2. Vesicles are covered by a protein coat that helps select cargo and facilitates membrane bending and vesicle formation. The coat also provides targeting to ensure vesicles fuse with the correct acceptor membrane.
3. Vesicle transport systems move materials through the cell in a regulated manner to allow for biosynthesis and organelle function. Defects in these transport pathways can lead to disease.
Proteins destined for secretion, integration in the plasma membrane, or inclusion in lysosomes generally share pathway that begins in the endoplasmic reticulum. Proteins destined for mitochondria, chloroplasts, or the nucleus use three separate mechanisms. And proteins destined for the cytosol simply remain where they are synthesized.
This document summarizes protein targeting mechanisms in cells. It discusses how signal sequences direct proteins to different organelles like the endoplasmic reticulum, mitochondria, chloroplasts and nucleus. The signal sequence is cleaved after the protein reaches its destination. Glycosylation in the ER plays a key role in targeting lysosomal enzymes. Mitochondrial and chloroplast proteins use a different targeting mechanism after full synthesis. Receptor-mediated endocytosis imports some extracellular proteins by binding to receptors and forming clathrin-coated vesicles.
This document summarizes protein targeting mechanisms in cells. It discusses how signal sequences direct proteins to different organelles like the endoplasmic reticulum, mitochondria, chloroplasts and nucleus. The signal sequence is cleaved after the protein reaches its destination. Glycosylation in the ER plays a key role in targeting lysosomal enzymes. Mitochondrial and chloroplast proteins use a different targeting mechanism after full synthesis. Receptor-mediated endocytosis imports some extracellular proteins by binding to receptors and forming clathrin-coated vesicles.
cell organelles- Endoplasmic reticulum and Golgi bodiesDivya S
The endoplasmic reticulum and golgi bodies are organelles that play important roles in protein synthesis and transport within cells. The endoplasmic reticulum acts as the site of protein synthesis and processing, and transports proteins to the golgi apparatus. The golgi apparatus further modifies and sorts proteins and lipids before packaging them into vesicles for transport within the cell or export from the cell. In this way, the endoplasmic reticulum and golgi apparatus work together to synthesize, process, and transport macromolecules within eukaryotic cells.
The document discusses cell differentiation and specialized cell functions. It states that the human body contains about 200 different cell types that are all derived from a single fertilized egg cell. During cell differentiation, cells undergo specialization where they synthesize specific proteins, change shape, and become efficient at specialized functions. For example, muscle cells elongate and accumulate actin and myosin, specializing in force generation. The document then discusses some main cellular functions performed by specialized cells and provides examples of membrane structure and organization in cells.
The document summarizes the endoplasmic reticulum (ER), an organelle found within eukaryotic cells. It was discovered in 1902 by Emilio Verrati but his work was initially disregarded. In the 1950s, Keith Porter and George Palade used electron microscopy to rediscover and prove the existence of the ER. The ER is a network of tubules and sacs that functions to fold and modify proteins. It is composed of rough ER with ribosomes on its surface for protein synthesis, and smooth ER involved in lipid and steroid production. Current research explores how ER stress contributes to diseases like neurodegenerative disorders, diabetes, and inflammation.
The document summarizes the endoplasmic reticulum (ER), an organelle found within eukaryotic cells. It was discovered in 1902 by Emilio Verrati but his work was initially disregarded. In the 1950s, Keith Porter and George Palade used electron microscopy to rediscover and prove the existence of the ER. The ER is a network of tubules and sacs that functions to produce and transport proteins and lipids. It exists in two forms: rough ER with ribosomes on its surface for protein synthesis, and smooth ER involved in lipid and steroid production. Current research explores how ER stress contributes to diseases like Alzheimer's, Parkinson's, and diabetes.
Proteins are the working molecules of cells that carry out functions encoded by genes. They include structural proteins, transport proteins, regulatory proteins, and signaling proteins. There are four levels of protein structure: primary, secondary, tertiary, and quaternary. Protein function derives from its three-dimensional structure, which is specified by the amino acid sequence. Chaperone proteins assist in protein folding to ensure proteins reach their correct native conformation. Post-translational modifications and interactions with ligands allow regulation of protein activity, while misfolded proteins are degraded through ubiquitination or lysosomal pathways.
Describe the similarities and differences (3 or 4 complete sentences.pdfpearlcoburnsanche303
Describe the similarities and differences (3 or 4 complete sentences) in the synthesis “pathway”
(i.e. all the organelles and cellular components involved) between a protein that is NOT secreted
(i.e., functions within the cytoplasm) versus a protein that IS secreted
Solution
The process of protein synthesis and secretion starts from the endoplasmic reticulum. The
polypeptide chain is formed in the ribosomes, and then transferred to the Golgi apparatus, where
the final modifications are done. The Golgi apparatus sorts the modified poly peptide molecules
and packages into new transport vesicles which reach their particular destinations.
The proteins that are intended to be used within the cell (intracellular proteins) are produced by
the ribosomes that float freely in the cytoplasm.
The proteins that are intended to be secreted out of the cell are synthesized by the ribosomes of
the RER. This system contains “cisternae.” They are the fluid filled sacs, into which the
synthesized proteins are released.
They modify these proteins by different processes. The proteins generally contain endoplasmic
reticulum signal sequence at their N-terminus, which directs them to the rough endoplasmic
reticulum. They enter into the endoplasmic reticulum as the lipid end of the protein (first 30
amino acids are hydrophobic) is attracted by the lipid component of the endoplasmic reticulum.
Once they are in the ER, the hydrophobic chain is removed by the enzymatic process. The
secretory proteins are transported to the Golgi apparatus for further modification. From the trans-
Golgi vesicles, proteins move to cell membrane through small transportation vesicles
(exocytosis). Some of then may be degraded by lysosomes as a part of regulation of gene
expression..
The document summarizes the organelles and structures found inside neurons. It notes that neurons resemble other cells but have distinctive shapes. The main organelles in neurons are the nucleus, cell body, dendrites, axon, ribosomes, endoplasmic reticulum, Golgi complex, lysosomes, mitochondria, and peroxisomes. Protein synthesis occurs via mRNA transcribed in the nucleus and transported to ribosomes. The endoplasmic reticulum modifies and transports proteins, while the Golgi apparatus further modifies proteins before they reach their destination. Gene expression can be regulated by controlling mRNA stability and degradation.
The document discusses the structure and functions of cell membranes. It notes that membranes are composed of phospholipids, glycolipids, cholesterol and proteins. Membranes form a selectively permeable barrier and establish concentration gradients. They localize enzymes and processes like transport, signaling, endocytosis and exocytosis. The fluid mosaic model describes membranes as a fluid structure with proteins embedded and diffusing. Membrane composition and fluidity impact functions like signaling, vesicle movement and cell division.
The endomembrane system consists of a network of membranes and organelles that transport molecules within the cell. It includes the endoplasmic reticulum, which has two types - rough ER involved in protein synthesis and smooth ER involved in functions like drug detoxification. The Golgi apparatus modifies and sorts proteins and lipids from the ER and transports them to other organelles or out of the cell. It contains a series of flattened sacs that process molecules as they move from its cis to trans sides.
COPI, COPII, and TRAPIII are protein complexes involved in vesicle transport between organelles. Vesicles bud from one organelle, are targeted to another using Rab GTPases and SNARE proteins, and fuse via SNARE pairing. The secretory pathway modifies and sorts proteins in the ER and Golgi before delivery to their final destinations, such as the plasma membrane, lysosomes, or secretory vesicles.
Protein sorting and targeting involves transporting proteins to the appropriate locations within or outside the cell. There are several pathways for protein targeting, including vesicular transport between organelles like the ER and Golgi, as well as transport of proteins into organelles like mitochondria and peroxisomes. Targeting signals like presequences and internal targeting peptides direct cellular transport machinery to correctly position proteins. Lipidation is another method to target proteins to specific membranes through modifications like glycosyl phosphatidylinositol anchors or myristoylation.
The document discusses membrane structure and function. It describes the fluid mosaic model of the plasma membrane, which depicts a bilayer of phospholipids with embedded and peripheral proteins. Membrane proteins allow the membrane to facilitate various transport mechanisms like passive diffusion, facilitated diffusion, and active transport via pumps and channels. Transport proteins move molecules across membranes through simple diffusion, facilitated diffusion using carrier proteins, osmosis, and active transport requiring ATP. Vesicles and bulk flow processes like endocytosis and exocytosis are also used to transport larger particles across the membrane.
The endomembrane system includes organelles like the nuclear envelope, endoplasmic reticulum, Golgi apparatus, lysosomes, vesicles, and plasma membrane. It works to modify, package, and transport lipids and proteins. The endoplasmic reticulum consists of rough and smooth regions that synthesize proteins and lipids. The Golgi apparatus further modifies and sorts proteins and lipids before they are transported to other organelles or released from the cell. Together, these membrane-bound organelles work cooperatively to process materials within eukaryotic cells.
The document discusses various pathways of protein trafficking in cells. It describes how proteins are targeted to different organelles like the endoplasmic reticulum, Golgi apparatus, mitochondria, chloroplasts, peroxisomes, and lysosomes. Proteins can be targeted co-translationally as they are synthesized or post-translationally after completion. The ER and Golgi play important roles in modifying proteins through folding, glycosylation and sorting before they are packaged into vesicles and transported to their final destinations. Defects in these trafficking pathways can lead to human diseases.
Structure and function of endoplasmic reticulum and golgi.pptxdivya1313
The document summarizes the structure and functions of the endoplasmic reticulum and Golgi bodies. It describes the ER as a network of membrane-enclosed channels involved in protein synthesis and processing. The Golgi body modifies and sorts proteins and lipids from the ER for transport within the cell or export. Vesicles transport proteins between organelles like the ER, Golgi body, and lysosomes for modification, sorting, and final destination.
1. Eukaryotic cells transport materials between membrane-bound organelles using vesicles that bud from donor membranes and fuse with acceptor membranes.
2. Vesicles are covered by a protein coat that helps select cargo and facilitates membrane bending and vesicle formation. The coat also provides targeting to ensure vesicles fuse with the correct acceptor membrane.
3. Vesicle transport systems move materials through the cell in a regulated manner to allow for biosynthesis and organelle function. Defects in these transport pathways can lead to disease.
Proteins destined for secretion, integration in the plasma membrane, or inclusion in lysosomes generally share pathway that begins in the endoplasmic reticulum. Proteins destined for mitochondria, chloroplasts, or the nucleus use three separate mechanisms. And proteins destined for the cytosol simply remain where they are synthesized.
This document summarizes protein targeting mechanisms in cells. It discusses how signal sequences direct proteins to different organelles like the endoplasmic reticulum, mitochondria, chloroplasts and nucleus. The signal sequence is cleaved after the protein reaches its destination. Glycosylation in the ER plays a key role in targeting lysosomal enzymes. Mitochondrial and chloroplast proteins use a different targeting mechanism after full synthesis. Receptor-mediated endocytosis imports some extracellular proteins by binding to receptors and forming clathrin-coated vesicles.
This document summarizes protein targeting mechanisms in cells. It discusses how signal sequences direct proteins to different organelles like the endoplasmic reticulum, mitochondria, chloroplasts and nucleus. The signal sequence is cleaved after the protein reaches its destination. Glycosylation in the ER plays a key role in targeting lysosomal enzymes. Mitochondrial and chloroplast proteins use a different targeting mechanism after full synthesis. Receptor-mediated endocytosis imports some extracellular proteins by binding to receptors and forming clathrin-coated vesicles.
cell organelles- Endoplasmic reticulum and Golgi bodiesDivya S
The endoplasmic reticulum and golgi bodies are organelles that play important roles in protein synthesis and transport within cells. The endoplasmic reticulum acts as the site of protein synthesis and processing, and transports proteins to the golgi apparatus. The golgi apparatus further modifies and sorts proteins and lipids before packaging them into vesicles for transport within the cell or export from the cell. In this way, the endoplasmic reticulum and golgi apparatus work together to synthesize, process, and transport macromolecules within eukaryotic cells.
The document discusses cell differentiation and specialized cell functions. It states that the human body contains about 200 different cell types that are all derived from a single fertilized egg cell. During cell differentiation, cells undergo specialization where they synthesize specific proteins, change shape, and become efficient at specialized functions. For example, muscle cells elongate and accumulate actin and myosin, specializing in force generation. The document then discusses some main cellular functions performed by specialized cells and provides examples of membrane structure and organization in cells.
The document summarizes the endoplasmic reticulum (ER), an organelle found within eukaryotic cells. It was discovered in 1902 by Emilio Verrati but his work was initially disregarded. In the 1950s, Keith Porter and George Palade used electron microscopy to rediscover and prove the existence of the ER. The ER is a network of tubules and sacs that functions to fold and modify proteins. It is composed of rough ER with ribosomes on its surface for protein synthesis, and smooth ER involved in lipid and steroid production. Current research explores how ER stress contributes to diseases like neurodegenerative disorders, diabetes, and inflammation.
The document summarizes the endoplasmic reticulum (ER), an organelle found within eukaryotic cells. It was discovered in 1902 by Emilio Verrati but his work was initially disregarded. In the 1950s, Keith Porter and George Palade used electron microscopy to rediscover and prove the existence of the ER. The ER is a network of tubules and sacs that functions to produce and transport proteins and lipids. It exists in two forms: rough ER with ribosomes on its surface for protein synthesis, and smooth ER involved in lipid and steroid production. Current research explores how ER stress contributes to diseases like Alzheimer's, Parkinson's, and diabetes.
Proteins are the working molecules of cells that carry out functions encoded by genes. They include structural proteins, transport proteins, regulatory proteins, and signaling proteins. There are four levels of protein structure: primary, secondary, tertiary, and quaternary. Protein function derives from its three-dimensional structure, which is specified by the amino acid sequence. Chaperone proteins assist in protein folding to ensure proteins reach their correct native conformation. Post-translational modifications and interactions with ligands allow regulation of protein activity, while misfolded proteins are degraded through ubiquitination or lysosomal pathways.
Describe the similarities and differences (3 or 4 complete sentences.pdfpearlcoburnsanche303
Describe the similarities and differences (3 or 4 complete sentences) in the synthesis “pathway”
(i.e. all the organelles and cellular components involved) between a protein that is NOT secreted
(i.e., functions within the cytoplasm) versus a protein that IS secreted
Solution
The process of protein synthesis and secretion starts from the endoplasmic reticulum. The
polypeptide chain is formed in the ribosomes, and then transferred to the Golgi apparatus, where
the final modifications are done. The Golgi apparatus sorts the modified poly peptide molecules
and packages into new transport vesicles which reach their particular destinations.
The proteins that are intended to be used within the cell (intracellular proteins) are produced by
the ribosomes that float freely in the cytoplasm.
The proteins that are intended to be secreted out of the cell are synthesized by the ribosomes of
the RER. This system contains “cisternae.” They are the fluid filled sacs, into which the
synthesized proteins are released.
They modify these proteins by different processes. The proteins generally contain endoplasmic
reticulum signal sequence at their N-terminus, which directs them to the rough endoplasmic
reticulum. They enter into the endoplasmic reticulum as the lipid end of the protein (first 30
amino acids are hydrophobic) is attracted by the lipid component of the endoplasmic reticulum.
Once they are in the ER, the hydrophobic chain is removed by the enzymatic process. The
secretory proteins are transported to the Golgi apparatus for further modification. From the trans-
Golgi vesicles, proteins move to cell membrane through small transportation vesicles
(exocytosis). Some of then may be degraded by lysosomes as a part of regulation of gene
expression..
The document summarizes the organelles and structures found inside neurons. It notes that neurons resemble other cells but have distinctive shapes. The main organelles in neurons are the nucleus, cell body, dendrites, axon, ribosomes, endoplasmic reticulum, Golgi complex, lysosomes, mitochondria, and peroxisomes. Protein synthesis occurs via mRNA transcribed in the nucleus and transported to ribosomes. The endoplasmic reticulum modifies and transports proteins, while the Golgi apparatus further modifies proteins before they reach their destination. Gene expression can be regulated by controlling mRNA stability and degradation.
The document discusses the structure and functions of cell membranes. It notes that membranes are composed of phospholipids, glycolipids, cholesterol and proteins. Membranes form a selectively permeable barrier and establish concentration gradients. They localize enzymes and processes like transport, signaling, endocytosis and exocytosis. The fluid mosaic model describes membranes as a fluid structure with proteins embedded and diffusing. Membrane composition and fluidity impact functions like signaling, vesicle movement and cell division.
The endomembrane system consists of a network of membranes and organelles that transport molecules within the cell. It includes the endoplasmic reticulum, which has two types - rough ER involved in protein synthesis and smooth ER involved in functions like drug detoxification. The Golgi apparatus modifies and sorts proteins and lipids from the ER and transports them to other organelles or out of the cell. It contains a series of flattened sacs that process molecules as they move from its cis to trans sides.
COPI, COPII, and TRAPIII are protein complexes involved in vesicle transport between organelles. Vesicles bud from one organelle, are targeted to another using Rab GTPases and SNARE proteins, and fuse via SNARE pairing. The secretory pathway modifies and sorts proteins in the ER and Golgi before delivery to their final destinations, such as the plasma membrane, lysosomes, or secretory vesicles.
Protein sorting and targeting involves transporting proteins to the appropriate locations within or outside the cell. There are several pathways for protein targeting, including vesicular transport between organelles like the ER and Golgi, as well as transport of proteins into organelles like mitochondria and peroxisomes. Targeting signals like presequences and internal targeting peptides direct cellular transport machinery to correctly position proteins. Lipidation is another method to target proteins to specific membranes through modifications like glycosyl phosphatidylinositol anchors or myristoylation.
The document discusses membrane structure and function. It describes the fluid mosaic model of the plasma membrane, which depicts a bilayer of phospholipids with embedded and peripheral proteins. Membrane proteins allow the membrane to facilitate various transport mechanisms like passive diffusion, facilitated diffusion, and active transport via pumps and channels. Transport proteins move molecules across membranes through simple diffusion, facilitated diffusion using carrier proteins, osmosis, and active transport requiring ATP. Vesicles and bulk flow processes like endocytosis and exocytosis are also used to transport larger particles across the membrane.
Describing and Interpreting an Immersive Learning Case with the Immersion Cub...Leonel Morgado
Current descriptions of immersive learning cases are often difficult or impossible to compare. This is due to a myriad of different options on what details to include, which aspects are relevant, and on the descriptive approaches employed. Also, these aspects often combine very specific details with more general guidelines or indicate intents and rationales without clarifying their implementation. In this paper we provide a method to describe immersive learning cases that is structured to enable comparisons, yet flexible enough to allow researchers and practitioners to decide which aspects to include. This method leverages a taxonomy that classifies educational aspects at three levels (uses, practices, and strategies) and then utilizes two frameworks, the Immersive Learning Brain and the Immersion Cube, to enable a structured description and interpretation of immersive learning cases. The method is then demonstrated on a published immersive learning case on training for wind turbine maintenance using virtual reality. Applying the method results in a structured artifact, the Immersive Learning Case Sheet, that tags the case with its proximal uses, practices, and strategies, and refines the free text case description to ensure that matching details are included. This contribution is thus a case description method in support of future comparative research of immersive learning cases. We then discuss how the resulting description and interpretation can be leveraged to change immersion learning cases, by enriching them (considering low-effort changes or additions) or innovating (exploring more challenging avenues of transformation). The method holds significant promise to support better-grounded research in immersive learning.
The cost of acquiring information by natural selectionCarl Bergstrom
This is a short talk that I gave at the Banff International Research Station workshop on Modeling and Theory in Population Biology. The idea is to try to understand how the burden of natural selection relates to the amount of information that selection puts into the genome.
It's based on the first part of this research paper:
The cost of information acquisition by natural selection
Ryan Seamus McGee, Olivia Kosterlitz, Artem Kaznatcheev, Benjamin Kerr, Carl T. Bergstrom
bioRxiv 2022.07.02.498577; doi: https://doi.org/10.1101/2022.07.02.498577
ESA/ACT Science Coffee: Diego Blas - Gravitational wave detection with orbita...Advanced-Concepts-Team
Presentation in the Science Coffee of the Advanced Concepts Team of the European Space Agency on the 07.06.2024.
Speaker: Diego Blas (IFAE/ICREA)
Title: Gravitational wave detection with orbital motion of Moon and artificial
Abstract:
In this talk I will describe some recent ideas to find gravitational waves from supermassive black holes or of primordial origin by studying their secular effect on the orbital motion of the Moon or satellites that are laser ranged.
The debris of the ‘last major merger’ is dynamically youngSérgio Sacani
The Milky Way’s (MW) inner stellar halo contains an [Fe/H]-rich component with highly eccentric orbits, often referred to as the
‘last major merger.’ Hypotheses for the origin of this component include Gaia-Sausage/Enceladus (GSE), where the progenitor
collided with the MW proto-disc 8–11 Gyr ago, and the Virgo Radial Merger (VRM), where the progenitor collided with the
MW disc within the last 3 Gyr. These two scenarios make different predictions about observable structure in local phase space,
because the morphology of debris depends on how long it has had to phase mix. The recently identified phase-space folds in Gaia
DR3 have positive caustic velocities, making them fundamentally different than the phase-mixed chevrons found in simulations
at late times. Roughly 20 per cent of the stars in the prograde local stellar halo are associated with the observed caustics. Based
on a simple phase-mixing model, the observed number of caustics are consistent with a merger that occurred 1–2 Gyr ago.
We also compare the observed phase-space distribution to FIRE-2 Latte simulations of GSE-like mergers, using a quantitative
measurement of phase mixing (2D causticality). The observed local phase-space distribution best matches the simulated data
1–2 Gyr after collision, and certainly not later than 3 Gyr. This is further evidence that the progenitor of the ‘last major merger’
did not collide with the MW proto-disc at early times, as is thought for the GSE, but instead collided with the MW disc within
the last few Gyr, consistent with the body of work surrounding the VRM.
Mending Clothing to Support Sustainable Fashion_CIMaR 2024.pdfSelcen Ozturkcan
Ozturkcan, S., Berndt, A., & Angelakis, A. (2024). Mending clothing to support sustainable fashion. Presented at the 31st Annual Conference by the Consortium for International Marketing Research (CIMaR), 10-13 Jun 2024, University of Gävle, Sweden.
PPT on Direct Seeded Rice presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
Sexuality - Issues, Attitude and Behaviour - Applied Social Psychology - Psyc...PsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Microbial interaction
Microorganisms interacts with each other and can be physically associated with another organisms in a variety of ways.
One organism can be located on the surface of another organism as an ectobiont or located within another organism as endobiont.
Microbial interaction may be positive such as mutualism, proto-cooperation, commensalism or may be negative such as parasitism, predation or competition
Types of microbial interaction
Positive interaction: mutualism, proto-cooperation, commensalism
Negative interaction: Ammensalism (antagonism), parasitism, predation, competition
I. Mutualism:
It is defined as the relationship in which each organism in interaction gets benefits from association. It is an obligatory relationship in which mutualist and host are metabolically dependent on each other.
Mutualistic relationship is very specific where one member of association cannot be replaced by another species.
Mutualism require close physical contact between interacting organisms.
Relationship of mutualism allows organisms to exist in habitat that could not occupied by either species alone.
Mutualistic relationship between organisms allows them to act as a single organism.
Examples of mutualism:
i. Lichens:
Lichens are excellent example of mutualism.
They are the association of specific fungi and certain genus of algae. In lichen, fungal partner is called mycobiont and algal partner is called
II. Syntrophism:
It is an association in which the growth of one organism either depends on or improved by the substrate provided by another organism.
In syntrophism both organism in association gets benefits.
Compound A
Utilized by population 1
Compound B
Utilized by population 2
Compound C
utilized by both Population 1+2
Products
In this theoretical example of syntrophism, population 1 is able to utilize and metabolize compound A, forming compound B but cannot metabolize beyond compound B without co-operation of population 2. Population 2is unable to utilize compound A but it can metabolize compound B forming compound C. Then both population 1 and 2 are able to carry out metabolic reaction which leads to formation of end product that neither population could produce alone.
Examples of syntrophism:
i. Methanogenic ecosystem in sludge digester
Methane produced by methanogenic bacteria depends upon interspecies hydrogen transfer by other fermentative bacteria.
Anaerobic fermentative bacteria generate CO2 and H2 utilizing carbohydrates which is then utilized by methanogenic bacteria (Methanobacter) to produce methane.
ii. Lactobacillus arobinosus and Enterococcus faecalis:
In the minimal media, Lactobacillus arobinosus and Enterococcus faecalis are able to grow together but not alone.
The synergistic relationship between E. faecalis and L. arobinosus occurs in which E. faecalis require folic acid
1. Video 13:
Introduction to the
Endomembrane System
Gergely, Z.R., Martinez, D.E., Donohoe, B.S. et al. J of Biol Res-Thessaloniki
25, 15 (2018). https://doi.org/10.1186/s40709-018-0086-2
2. The Endomembrane
System Derived from the
cytoplasmic membrane
and forming a
coordinated unit
Include the ER, Golgi,
endosomes,
lysosomes, and
vacuoles (NOT the
mitochondria and
chloroplasts)
Allow transportation of
proteins, lipids, and
complex
polysaccharides
3. Transport System
Transport vesicles
allow movement
between cellular
compartments
Travel along the
cytoskeleton mediated
by motor proteins
Sorting signals within
amino acid sequences
or oligosaccharides
allow targeting to
appropriate cellular
compartment
4. Transport Pathways
All begin with the the
biosynthetic pathway
Proteins produced in
RER
●
Vesicles released
from RER fuse with
the cis Golgi
complex,
undergoing further
modifications
●
Transport vesicles
released from the
trans Golgi
Karp’s Cell & Molecular Biology (2020) Fig 8.2
5. Transport Pathways
Secretory pathways
result in exocytosis and
may be constitutive
(continuous) or
regulated (require
signal for release)
Materials are also
imported through
endocytosis and
digested within the
lysosome
Karp’s Cell & Molecular Biology (2020) Fig 8.2
8. Other Experimental
Approaches
Subcellular fractionation (differential centrifugation)
●
Idenification of fraction containing particular enzymes or
functions
●
Now extend cell-free systems to include synthetic
liposomes
Effects of genetic mutations
●
Introduction of mutations in identify function of particular
gene
●
Newer methods include RNA interference and CRISPR
10. The Endoplasmic
Reticulum
Likely from invagination
of cytoplasmic
membrane
Differentiated into rough
and smooth due
to presence
or absence of
bound ribosomes
on the
cytoplasmic
surface
11. ER Similarities
RER and SER are joined, having a
continual luminal space which
allows for free diffusion
Number of
proteins are
common to both
RER & SER
Both synthesize
some shared
lipids and
cholesterol
Karp’s Cell & Molecular Biology Fig. 8.10
12. Highly curved, tubular network with large numbers of
reticulons (cause bending of the membranes)
Karp’s Cell & Molecular Biology Fig. 8.10
Smooth Endoplasmic
Reticulum
Detoxification of drugs
such as ethanol and
barbituates in the liver
by oxygenases
Ca2+ sequestering in
muscle cells (called
sarcoplasmic reticulum)
Synthesis of steroidal hormones in
endocrine cells
13. Continuous with the outer nuclear membrane and
composed of flattened sacs (cisternae) connected by
helical “ramps”
Karp’s Cell & Molecular Biology Fig. 8.10
Rough Endoplasmic
Reticulum
Increased in secretory cells
(acinar cells of pancreas &
mucous cells in digestive
tract)
The site of synthesis of the
majority of phospholipids for
inclusion in cellular
membranes
14. Karp’s Cell & Molecular Biology Fig. 8.10
Rough Endoplasmic
Reticulum
Undergo co-translational
translocation from bound
ribosomes to ER lumen
Synthesizes carbohydrate
chains and initiates N-
linked glycosylation of
proteins
Site of synthesis of approx. 1/3 of cellular proteins: those
destined for secretion or inclusion in endomembrane
organelles, integral
membrane proteins
15. Membrane-bound or Free
Ribosome?
Remainder of proteins are synthesized by free
(cytoplasmic) ribosomes
●
Cytosolic proteins
●
Peripheral membrane proteins for cytosolic surface)
●
Nuclear proteins (contain nuclear localization signals)
●
Proteins for other organelles (lysosomes, mitochondria,
chloroplasts)
All translation is initiated on free ribosomes
Proteins which should go to ER contain an N-terminal
signal sequence at N-terminus: results in ribosome
binding to ER surface and co-translational translocation
16. Co-translational Translocation
SRP binds signal sequence and guides ribosome to
translocon channel protein by binding to the SRP
receptor
SRP = signal recognition particle
Karp’s Cell & Molecular Biology Fig. 8.13
Polypeptide binding to translocon opens
“plug” to allow polypeptide to enter ER
Signal removal
and folding
17. Synthesis of Integral Proteins
Hydrophobic “stop-transfer” sequence blocks
translocation into ER lumen
The next steps dependent upon location of positive and
negative charges at ends of the transmembrane region
Karp’s Cell & Molecular Biology Fig. 8.14
●
If N-terminus side is
negative, the lateral gate
of the translocon allows
the transmembrane
region to migrate into the
membrane
●
Results in C-terminus on
cytosolic side
18. Synthesis of Integral Proteins
●
If N-terminus side is positive, the translocon first
reorients the transmembrane region, which is then able
to migrate through the lateral gate
●
This results in the N-terminus being located on the
cytosolic side
●
Multi-pass polypeptides utilize translocon many times in
an antiparallel
manner
●
Some proteins
utilize
alternative
pathways
Karp’s Cell & Molecular Biology Fig. 8.14
20. Protein
Processing
Many secretory cells have a
polarized or directional structure
Reflects movement of
polypeptides from synthesis in the
RER, processing in the RER &
Golgi, and secretion via transport
vesicles or secretory granules
Processing is a highly regulated
multi-step process required for
the production of proteins
(biologically-active form)
Karp’s Cell & Molecular Biology Fig 8.12
21. Protein
Processing
Removal of signal peptide by
signal peptidase
Protein folding & molecular
chaperones
Formation and shuffling of
disulfide bonds by disulfide
isomerase
Addition of carbohydrates by
oligosaccharyltransferase
24. Membrane
Asymmetry
Cellular membranes “grow”
rather than being produced
through de novo synthesis
Protein and lipid
composition are altered as
membranes are moved from
one compartment to the next
Through the means of
membrane fusion, specific
asymmetry of membrane is
maintained
Karp’s Cell & Molecular Biology Fig 8.15
25. Altering Lipid
Composition
Karp’s Cell & Molecular Biology Fig 8.16
Enzymatic
conversion
Preferential
inclusion of
specific lipids
within vesicles
Movement from one
compartment to another by lipid
transfer proteins
Newly synthesized
lipids are inserted
in cytosolic leaflet,
but may be moved
by flippases
26. Glycosylation
Majority of proteins produced in the RER become
glycoproteins: starts in the RER & completed in the Golgi
Addition of sugars to oligosaccaride
catalyzed by specific
glycosyltransferases
●
Transfer a monosaccharide
from a nucleotide sugar
Oligosaccharide first synthesized
on dolichol phosphate
Transferred to protein by
oligosaccharyltransferase
enzyme
28. Modification & Quality Control
Following
acquisition,
two
terminal
glucose
residues
removed
Bound by calnexin or
calreticulin (chaperone)
Final glucose removed
Karp’s Cell & Molecular Biology Fig 8.18
29. Modification & Quality Control
Conformation-sensing
enzyme (UGGT) determines
whether it is misfolded based
upon whether hydrophobic
regions are exposed
Karp’s Cell & Molecular Biology Fig 8.18
30. Modification & Quality Control
Eventually, a mannose is
removed & it is
transported to proteasome
for destruction
Karp’s Cell & Molecular Biology Fig 8.18
If it is
misfolded,
glucose
residue
again
added and
cycle
repeated
31. Transport from ER to Golgi
Special exit sites on edges of ER lack ribosomes and are
sites of vesicle budding
These small vesicles fuse together to form larger transport
vesicles and interconnected tubules
Vesicular-tubule carriers (VTCs) move towards the Golgi
complex and fuse with the cis-Golgi network
●
VTC transport occurs via microtubule tracks
The Golgi will allow for further modification of proteins and
sorting for final transport
32. Video 16:
Golgi Complex &
Transport
https://www.cancer.gov/about-nci/organization/dcb/research-programs
33. Golgi Complex
Tubule networks on cis and trans faces are involved in
sorting of proteins:
●
cis will send back to ER or on to the cisternae
●
trans will sort to plasma membrane or intracellular
organelles
34. Golgi Complex
Golgi cisternae are involved in the sequential modification
of the proteins synthesized by the ER
●
Differential composition in each compartment
Osmium
tetroxide
stains
unsaturated
fatty acids
in the Cis
Cisternae
Mannosidase II enzyme
in the Medial Cisternae
Nucleoside
diphosphatase
Enzyme in the
Trans
Cisternae
35. Golgi Complex
Alters the N-linked oligosaccharides added within the ER
as they progress through the cisternae
Assembles O-linked oligosaccarides
Majority of
complex
polysaccharide
assembly
Different
enzymes
found in each
compartment
36. Glycosylation
Enzymes involved in glycosylation are integral proteins
with active sites facing the interior of the Golgi
Those involved in adding sugars are transferases
Karp’s Cell and Molecular Biology (2020) Fig. 8.23
37. Vesicular Transport Model
Popular in the 1980s & 90s
Vesicles move from one
cisternae to the next, while
the cisternae themselves are
“static”
In vitro evidence of budding
and fusing vesicles
Believed to occur in vivo in
an anterograde direction
Karp’s Cell and Molecular Biology (2020)
Fig. 8.24
38. Cisternal Maturation Model
First & currently accepted
Cisternae contents change
over time and develop in an
anterograde direction
Vesicles travel in retrograde:
are they returning enzymes?
Could both potentially be
occurring?
Karp’s Cell and Molecular Biology (2020)
Fig. 8.24
39. Transport from ER
to Golgi:Revisited
ERGIC = ER Golgi intermediate
compartment
Comprised of the larger vesicles & tubules
formed through the fusion of transport
vesicles
3 kinds of coated transport vesicles:
●
COPI = posterograde from Golgi
●
COPII = anterograde from ER
●
Clathrin-coated = from plasma membrane
& trans Golgi network to other organelles
Karp’s Cell and Molecular Biology (2020)
Fig. 8.26
40. Coated Vesicles
Transport vesicles are
coated in proteins which
mediate
●
Membrane curvature
●
Selective uptake of cargo
●
Selective binding to target
compartment
Karp’s Cell and Molecular Biology (2020)
Fig. 8.25
41. COPII Vesicles
Karp’s Cell and Molecular Biology (2020)
Fig. 8.25
Form outer scaffold = framework
Remainder of
proteins are
inner layer of
adaptors
42. COPII Vesicles
Guanine exchange factor
catalyzes Sar1-GDP to
Sar1-GTP: implants into
cytoplasmic membrane of
RER: recruits Sec23-Sec24
Karp’s Cell and Molecular Biology (2020)
Fig. 8.26
Sec13-
Sec31
form outer
scaffold
Sec24 recruits
Golgi enzymes,
membrane
proteins for
docking/fusion,
and soluble
cargo receptors
43. Outer Vesicle
Coats
Karp’s Cell and Molecular Biology (2020) Fig. 8.28
Transport vesicle shapes and sizes
are dependent upon the external
coat proteins & their interactions
Disassemble &
released into
cytoplasm to allow
docking and fusion
For COPII, catalyzed
by hydrolysis of GTP
to GDP
44. COPI: Retrograde Transport
Karp’s Cell and Molecular Biology (2020) Fig. 8.29
●
Majority of ER-resident
proteins are retained and
unlikely to be included in
transport vesicles
●
Soluble ER-resident proteins
contain KDEL (lys-asp-glu-
leu) amino acid retrieval
sequence in C-terminus which
bind specific KDEL receptors
for return in COPI vesicle
●
Similarly KKXX signal used
for membrane proteins
●
Unique signals likely for
specific Golgi compartments
46. Sorting to the Membrane
Both secretory proteins &
cytoplasmic membrane
proteins must be targeted
to the cytoplasmic
membrane.
Both may be transported
through secretory vesicles
in the constitutive
pathway
Some secretory proteins
also follow regulated
pathways: aggregates in
granules require hormone
or nervous stimulus
Karp’s Cell & Molecular Biology (2020) Fig. 8.2
47. Targeting Vesicles
4 Steps: targeted transport, tethering, docking & fusion of
membranes
Karp’s Cell & Molecular Biology (2020) Fig. 8.32
Tethering may be through
fibrous or multiprotein
complexes
●
Specificity mediated
by G proteins called
Rabs
●
Rabs specific to
particular
compartments
Rabs also
recruit
motor
proteins
for
transport
through
cytoplasm
48. Targeting Vesicles
Docking due to interaction of v-SNARE & t-SNARE
Karp’s Cell & Molecular Biology (2020) Fig. 8.32
v-SNARE
t-SNARE
49. Model of Synaptic Vesicle
Exocytosis
Karp’s Cell & Molecular Biology (2020) Fig. 8.33
Synaptobrevin (v-SNARE) & Syntaxin (t-SNARE) both
contain transmembrane domains that anchor them to the
vesicle & plasma
membrane
Including
SNAP-25
(t-SNARE),
4 helix bundle
forms through
hydrophobic
interactions
50. Model of Synaptic Vesicle
Exocytosis
Karp’s Cell & Molecular Biology (2020) Fig. 8.33
●
For regulated release,
may stay in interlocked
formation until
stimulus received
●
Leads to formation of
a water-filled pore as a
transition state
●
Transmembrane
domains become
embedded in single
bilayer to form the
fusion pore
51. Synaptic Vesicle Exocytosis
Karp’s Cell & Molecular Biology (8th
ed) Fig. 4.57
●
Binding of Ca2+
by v-SNARE triggers fusion and release
of neurotransmitters
52. Exocytosis
Karp’s Cell & Molecular Biology (2020) Fig. 8.33
Contacts between vesicle & membrane result in pore
formation on outside of an alveolus
Fusion Pore
Fusion of vesicle and
plasma membrane
results in release of
contents into the
extracellular
environment
Luminal part of vesicle is
now on the surface of
the plasma membrane
53. Plant Cell Central Vacuoles
Karp’s Cell & Molecular Biology (2020) Fig. 8.38
Used for storage of
many biomoleucles
including sugars,
polysaccharides, &
amino acids
Tonoplast (membrane)
site of active transport of
ions to ensure turgor
pressure
Site of cellular digestion,
in lieu of lysosomes:
contain hydrolases
54. Posttranslational Uptake
The proteins destined
for organelles which are
not a part of the
endomembrane system
are synthesized by free
ribosomes
Following translation,
they are transported to
the target organelle
Relies on presence of
amino acid localization
signal
Organelles with
posttranslational uptake:
●
Peroxisomes
●
Nucleus
●
Mitochondria
●
Chloroplasts
Interaction of specific
chaperones or receptors
allow directed transport
from cytoplasm
Pore proteins regulate
entry into the organelle
55. Mitochondrial
Uptake
Majority of polypeptides
synthesized in cytoplasm
and transported in as
unfolded polypeptides by
specific chaperones.
Different amino acid
sequences interact with
different chaperones and
protein complexes to
determine appropriate
localization
Chaperones
TOM Complex
TIM Complex
Karp’s Cell & Molecular Biology (2020) Fig. 8.49
56. Mitochondrial Uptake
Binding of chaperones involved in targeting to TOM
complex on outer mitochondrial membrane
TOM receptor recognizes mitochondrial protein and
channel complex allows its translocation
Karp’s Cell & Molecular Biology (2020) Fig. 8.49
Location of a
positively
charged
localization
signal
determines
compartment
57. Mitochondrial Uptake
Internal sequence results in transport through the TIM22
complex = inner mitochondrial membrane protein
Karp’s Cell & Molecular Biology (2020) Fig. 8.49
A terminal
sequence
(presequence)
results in transfer
through TIM23 =
matrix protein
●
Bound by
mitochondrial
chaperones,
folded and
presequence
removed
58. Chloroplast Uptake
Karp’s Cell & Molecular Biology (2020) Fig. 8.50
Sequential import
through Toc and
Tic complexes
for entry into
the stroma
Stroma domain
removed
Also imported in unfolded state and interact with
molecular chaperones
Targeted through presence of the N-terminal transit
peptide
59. Chloroplast Uptake
Karp’s Cell & Molecular Biology (2020) Fig. 8.50
Chaperones assist
folding of stromal
proteins
Thylakoid transfer
domain allows
transfer into
membrane or
lumen
Some thylakoid
membrane
proteins synthesized
for direct insertion
61. Lysosomes
Are the digestive organelle
of the cell, containing
multiple acid hydrolases for
the digestion of:
●
Food particles
●
Extracellular debris
●
Pathogens
●
Biomolecule degradation
●
Autophagy
Proton transport used to
create acidic environment
Karp’s Cell & Molecular Biology (2020) Fig. 8.35
62. Autophagy
Digestion of cellular
organelles:
●
Turnover of worn out/
defective components
●
Source of biomolecules/
energy
●
Protection from
intracellular pathogens
●
Prevents accumulation
of specific cellular
components: protective
Karp’s Cell & Molecular Biology (2020) Fig. 8.37
Retained
indefinitely
63. Sorting of Lysosomal
Proteins
1)Mannose residue
phosphorylated in
the cis-Golgi
2)Incorporation into
clathrin-coated
vesicles
3)Mannose 6-
phosphate receptors
interact with
enzymes and
adaptors
Karp’s Cell & Molecular Biology (2020) Fig. 8.30
64. Clathrin-coated Vesicles
Mannose-6-P
acts as targeting
mechanism for
lysosomal
enzymes
Interaction of
receptor and/or
lysosomal
membrane
proteins with
adaptor
Adaptor also
required for
assembly of
clathrin coat
Karp’s Cell & Molecular Biology (2020) Fig. 8.30
65. Sorting of Lysosomal
Proteins
4) Clathrin coat &
receptors disassemble
5) Receptors return to
trans-Golgi
6) Develop into
endosomes, then
lysosomes
7) Secreted lysosomal
enzymes also
returned by mannose-
6-P receptors
Karp’s Cell & Molecular Biology (2020) Fig. 8.30
66. Cellular Importation
Endocytosis
involves the
importation of
extracellular
fluid, dissolved
solutes, &
suspended
macromolecules
●
May be bulk
phase (general)
or receptor-
mediated
(specific)
Karp’s Cell & Molecular Biology (2020) Fig. 8.39
Phagocytosis is the uptake of particulate matter
RECEPTOR-MEDIATED ENDOCYTOSIS
67. Clathrin Coat Assembly
Karp’s Cell & Molecular Biology (2020) Fig. 8.42
Assembly of clathrin coats
for both endocytosis and
lysosomal vesicles
involves interaction of
clathrin subunits and
adaptor proteins
69. Vesicle
Formation
Dynamin proteins
polymerize to form ring
around the “stalk” of the
forming vesicle
GTP hydrolysis leads to
separation of the vesicle
from the membrane
Blocking of hydrolysis
with analog shows helical
association of dynamin
Karp’s Cell & Molecular Biology (2020) Fig. 8.42
70. Endocytic Pathway
Karp’s Cell & Molecular Biology (2020) Fig. 8.42
Fate of receptors &
ligands are dependent
on their purpose
Housekeeping
receptors (red)
Ligands include needed
substances (eg. iron
and cholesterol)
●
Receptors are recycled
to the plasma
membrane
●
Ligands to late
endosomes
71. Endocytic Pathway
Karp’s Cell & Molecular Biology (2020) Fig. 8.42
Signaling receptors
(green)
Ligands include insulin
and growth factors
●
Both receptors &
ligands to late
endosomes
Late endosomes fuse
with additional vesicles
containing lysosomal
enzymes & fuse with
lysosomes
72. Phagocytosis
Food acquisition (unicellular organisms), immune cell
engulfment of pathogens
Karp’s Cell & Molecular Biology (2020) Fig. 8.48
Yeast
cell
Leukocyte
Some pathogens
escape digestion:
●
M. tuberculosis
prevents fusion
with lysosome
●
L. monocytogenes
phospholipases
allow escape from
lysosome into
cytoplasm
73. Entrapment of particle,
followed by engulfment
to form a phagosome
Fuse with a lysosome for
digestion: usable
nutrients transferred to
cytoplasm
Residual body forms and
contents released
through exocytosis or
retained permanently as
lipofuscin pigment
granule
Phagocytosis
Karp’s Cell & Molecular Biology (2020) Fig. 8.48
75. The Cytoskeleton
Divided into
three classes:
microfilaments
(actin),
intermediate
filaments (IFs),
and
microtubules
(MT)
Noncovalently
bonded protein
polymers:
highly dynamic
Microfilaments Microtubules
Merge
Intermediate
filaments
76. Major Functions
All three classes play
various roles in providing
structure and support
Microtubules act as
“tracks” for the movement
of organelles and
materials
Also a framework for
organization of organelles
Karp’s Cell & Molecular Biology (2020) Fig 9.1
77. Major Functions
Microtubule network and peroxisome transport
Peroxisomes
Peroxisomes
Peroxisomes
Karp’s Cell & Molecular Biology (2020) Fig 9.2
78. Major Functions
Microfilaments involved in growth
of axons
Also form the force-generating
apparatus for cell motility
Karp’s Cell & Molecular Biology (2020) Fig 9.1
79. Major Functions
Movement of chromosomes
Contractile ring for cytokinesis
Formation of the mitotic spindle
Karp’s Cell & Molecular Biology (2020) Fig 9.1
81. Microtubules
Karp’s Cell & Molecular Biology (2020) Fig 9.3
Plus End
Minus End
Protofilaments formed of
alternating a- and b-tubulin
subunits
Offset alignment
results in helical
structure
Plus end
(b-tubulin terminus)
and minus end
(a-tubulin terminus)
results in
microtubule
structural and
functional polarity
82. Microtubule-Associated
Proteins (MAPs)
Karp’s Cell & Molecular Biology (2020) Fig 9.4
Multiple other proteins typically associated with
microtubules
Roles in increasing
microtubule stability and
promoting assembly of
tubulin subunits
Many regulated by
phosphorylation
Alterations in Tau function linked
to various forms of dementia
83. Tau & Dementia
Debate: cause or effect of
Alzheimer’s?
Brain 2006 129(11):3035-3041
Hyperphosphorylated Tau protein incapable of binding
to microtubules: found in neurofibrillary tagles/plaques
84. Structural Support
Organization of microtubules determines the overall shape
of the cell:
●
Radial arrangement seen in cultured animal cells results
in round, flattened
shape
●
Basal to apical
arrangement in
columnar epithelial
cells
●
Lengthwise
arrangement along
axons
Karp’s Cell & Molecular Biology (2020) Fig 9.5
85. Structural Organization
Association with integral membrane proteins influences
organization
Cellulose synthase
association determines
location/orientation
of cellulose
microfibrils which
determines plant
cell shape and
manner of growth
Organelle localization
eg. Golgi apparatus
Karp’s Cell & Molecular Biology (2020) Fig 9.6
Cellulose synthase Microtubules
87. Intracellular Motility
Microtubule networks act as “roads” through the cell,
allowing specific transport of materials to a given target
Karp’s Cell & Molecular Biology (2020) Fig 9.7
Microtubule tracks
within for transport of
organelles, transport
vesicles and
molecules such as
mRNA & ribosomes
Neurofilaments
support
structure of
axons
88. Motor Proteins
Large variety of motor proteins in a given cell, each
specialized for a specific type of cargo
Three broad classes: kinesins, dyneins, & myosins
●
Both kinesins & dyneins use microtubule pathways
●
Myosins use microfilaments
Movement based on binding and hydrolysis of ATP to
cause conformational changes allowing stepwise
movement from one subunit to the next
89. Kinesins
Heads are highly conserved motor region: binding and
hydrolysis of ATP for movement along the microtubule
Tail sequences very diverse bind the cargo specific for that
particular type of kinesin
Karp’s Cell & Molecular Biology (2020) Fig 9.11
90. Kinesins
Each “step” requires the binding and hydrolysis of one
molecule of ATP
Rate of movement is dependent upon ATP concentration
Karp’s Cell & Molecular Biology (2020) Fig 9.11
91. Kinesins
The neck region of the molecule plays an important role in
“transmitting” the conformational changes from one head
subunit to the other
Majority of kinesins move toward the plus end of the
microtubule, but some do move toward the minus end
●
Neck region also determines the direction of movement
along the microtubule
Small group of kinesins are involved in microtubule
depolymerization instead: called microtubule
depolymerases
●
Critical in cell division processes
92. Kinesins & Organelle Transport
Normal Kinesin mutant
Normal
Microtubu
les
Mitochond
ria
Karp’s Cell & Molecular Biology (2020) Fig 9.12
93. Cytoplasmic Dynein
Dynein first discovered as the motor protein associated
with cilia and flagella
Karp’s Cell & Molecular Biology (2020) Fig 9.13
Composed of two identical
heavy chains
Involved in positioning of
spindle & chromosome
movement
Transport towards
minus end of the microtubule:
positioning of centrosomes &
Golgi, and in various transport
94. Cellular
Transport
Model for use of
kinesins and dyneins
in cellular transport
based upon
microtubule polarity
Vesicles may have
both types bound at
one time: inactive vs
active forms, or a tug-
of-war?
Karp’s Cell & Molecular Biology (2020) Fig 9.13
96. Microtubule-Organizing
Centers (MTOCs)
Specialized structure where the initial formation (or
nucleation) of a small section of the microtubule occurs,
followed by its rapid elongation
MTOCs include:
●
Centrosomes
●
Basal body: associated with cilia/flagella & similar to
centrosomes
●
Plant MTOC: more dispersed on outer surface of
nuclear envelope
97. The Centrosome
Karp’s Cell & Molecular Biology (2020) Fig 9.14
Contains two barrel-shaped
centrioles surrounded by electron
dense pericentriolar material (PCM)
Major site of microtubule initiation in
animal cells & is the centre of the
cell’s microtubule network
98. Nucleation
Karp’s Cell & Molecular Biology (2020) Fig 9.15
Microtubules always assembled with the minus end
associated with the centrosome
Growth occurs
through the
addition of
tubulin dimers
to the plus end
May remain
associated or
severed and
anchored in
other regions
of the cell
99. Nucleation
Karp’s Cell & Molecular Biology (2020) Fig 9.16
Ring of 13 g-tubulin monomers in complex
with additional proteins at site of nucleation
g-tubulin, a/b-tubulin, DNA
100. Microtubule Dynamics
Karp’s Cell & Molecular Biology (2020) Fig 9.17
Noncovalent association of dimers allows rapid
reorganization or polymerization/depolymerization
as needed
Interphase
Preprophase
band: future
division plane
Mitotic
spindle
formation
Phragmoplast:
cell wall
formation
between cells
101. Role of GTP
Karp’s Cell & Molecular Biology (2020) Fig 9.21
b-tubulin is a GTPase and
must be bound to GTP for
polymerization to occur
GTP is hydrolyzed shortly
after polymerization
GDP-bound tubulin lacks
stability on its own, & will
rapidly depolymerize in the
absence of MAPs
Structural cap model
describes effect
102. Dynamic Instability
Karp’s Cell & Molecular Biology (2020) Fig 9.24
Plus-end tracking
proteins (+TIPs) bind to
ends of microtubules to
regulate rate of growth or
shrinkage
+TIPs mediate
attachment to structures
(eg. kinetochores, actin)
Growing & shrinking microtubules found within the same
region of the cell
Rapid shift between growing & shrinking phases
103. Video 22:
Cilia & Flagella
https://www.mdpi.com/2313-7673/3/2/5/htm
104. Cilia & Flagella
Hair-like cellular projections which are usually motile
Both are constructed from microtubules in the same
fashion
Both may be used for cellular motility by unicellular
organisms, and flagella present on animal gametes
Differentiation based upon cell type and type of motion
105. Cilia
Single, non-motile cilium
on almost all cells used
as sensory “antennae”
Used for cellular motility, but also found on
surface of non-motile cells for the purpose of
moving extracellular materials
Use a coordinated oar-like
motion
Karp’s Cell & Molecular Biology (2020) Fig 9.25
& 9.26
106. Flagella
Karp’s Cell & Molecular Biology (2020) Fig 9.27
Found in singles or pairs
for locomotion
Variety of patterns of
motions, including
assymetric waveforms and
symmetrical propellar-like
movements
107. Cilia/Flagella Structure
Karp’s Cell & Molecular Biology (2020) Fig 9.30
Membrane is continuous with the plasma membrane
Basal body is an
MTOC identical to
the centriole
Primary cilium
derived from
centriole, new basal
bodies in secondary
cilia
A and B tubules of
basal body form
doublets of the
axoneme
108. Karp’s Cell & Molecular Biology (2020) Fig 9.28
Axoneme is the core structure of
longitudinal microtubules and associated
proteins
Axoneme Structure
9 peripheral doublets
surrounding 2 central
single microtubules
(9 + 2 array)
Central sheath connects
to A tubules by radial
spoke proteins
109. Karp’s Cell & Molecular Biology (2020) Fig 9.28 & 9.29
Axoneme Structure
Nexin-dynein
regulatory
complex
(N-DRC)
Movement of outer & inner
axonemal dynein arms result in
bending motion of flagella/cilia
110. Karp’s Cell & Molecular Biology (2020) Fig 9.31
Intraflagellar
Transport
Growth occurs only at the
(+) end
Transport uses IFT
particles (protein
complexes) to carry
tubulin or other cargo
Kinesin transports
outward, and cytoplasmic
dynein inward
111. Karp’s Cell & Molecular Biology (2020) Fig 9.32 & 9.33
Mechanism
Dynein stem is
anchored to the
A tubule
Movement due to binding
& release of dynein heads
1) Heads bind to B tubule
2) Conformational change in dynein
causes sliding of anchored doublet
3) Heads release B tubule allowing
return to original position
4) Cycle repeats
Nexin bridges results in limited
movement and bending
112. Karp’s Cell & Molecular Biology (2020) Fig 9.34
Sliding Mechanism
Central position occurs when outer
doublets are all at the same level
Sliding of doublets in relation
to the position of its
neighbours will
determine the direction
of bending
Inner tubules slide towards base
of the cilium/flagellum
*Different positional relationships can
result in different stroke patterns
114. Intermediate Filaments
Provide mechanical strength to the cells, particularly those which
undergo large amounts of stress (nerves, muscles, epithelia)
Only in animals so far, but other insoluble fibres of diverse
protein sequences found in other eukaryotes
Chemically heterogeneous, with approx. 70 different genes in
humans
●
All of similar structure: solid & unbranched with 10-12 nm
diameter
●
5 classes based on cell type of expression, and biochemical,
genetic, and immuonologic criteria
– Cytoplasmic filaments (Types I – IV)
– Lamins (Type V): support nuclear membrane
115. IF Structure All IFs share same basic
structure:
●
a-helical central fibrous
domain: homologous
sequences
●
Terminal globular domains
of variable size/sequence
●
Different N- and C-terminal
sequences and their
association together results
in polarity within the dimers
●
Anti-parallel association of
dimers into nonpolar
tetramer = basic unit
Karp’s Cell & Molecular Biology Fig 9.36
116. IF Structure ●
Subunits associate in
groups of 8 to form a unit
length
●
End-to-end association to
form the polymerized IF
●
Growth through
intercalation within
existing IF
●
Polymerization &
depolymerization
regulated through
phosphorylation
●
Only cytoskeletal fibres
that lack polarity
Karp’s Cell & Molecular Biology Fig 9.36
~60 nm
117. Cytoplasmic IFs
Include proteins
such as keratin
(epithelia),
desmin (muscle),
and the
neurofilaments
(CNS and PNS
nerves)
Interconnected to
other cytoskeletal
filaments by
plectin cross-
bridges
Karp’s Cell & Molecular Biology Fig. 9.35
118. Epithelial Cells IFs (Types I and II) are
composed of keratin
Found radiating
throughout the cell
Often terminate on
desmosomes
(communication points
between cells)
Karp’s Cell & Molecular Biology Fig. 9.43 & 7.27
119. At least three different
proteins (Type IV Ifs)
Unique in structure
due to presence of
sidearms : ensure
appropriate spacing
between parallel fibres
Increasing amounts of
IFs as neuron matures
Karp’s Cell & Molecular Biology Fig. 9.43 & 7.27
Neurofilaments
120. Lamins
Form a strong,
mesh-like grid on
the nucleoplasmic
side of the inner
nuclear membrane
called the nuclear
lamina
Disassembled
during prophase of
mitosis/meiosis
124. Microfilaments
Assembled from monomers into
polar fibre with “barbed” and
“pointed” ends
Organized into:
●
Ordered arrays
●
Highly branched networks
●
Tightly anchored bundles
Karp’s Cell & Molecular Biology (2020) Fig 9.39
(+) “barbed”
end
(-) “pointed”
end
125. Assembly &
Disassembly
Regulated through
presence of ATP/ADP with
hydrolysis after
incorporation
Critical concentration for
the addition of ATP-actin
to either end is different:
lower concentrations
required for addition to
(+) end
At 0.3 mM (-) end removal
= (+) end addition
Karp’s Cell & Molecular Biology (2020) Fig 9.41
126. Myosin
Karp’s Cell & Molecular Biology (2020) Fig 9.43
Superfamily of motor proteins which
associate with actin filaments
Minimum of 17 classes
identified, with about 40
different myosins in humans
Type II (conventional)
myosins first identified
in muscle
Actin subunit
comprised of 6
polypeptide
chains
ATP-binding
cleft & motor
function
associated with
the head
127. Myosin Type II Filaments
Karp’s Cell & Molecular Biology (2020) Fig 9.45
Tails associate with
heads on either end to
form a bipolar filament
Myosin moves towards
(+) end of the
microfilament
Bipolar arrangement
results in
microfilaments being
pulled towards one
another
128. Unconvensional Myosins
Karp’s Cell & Molecular Biology (2020) Fig 9.61
Do not form filaments
and generally operate
independently
Myosin I has a single
head and acts as
attachment point for
microfilaments to the
plasma membrane
●
Potential involvement
in the alteration of
membrane shape
129. Unconvensional
Myosins
Karp’s Cell & Molecular Biology (2020) Fig 9.46
Many involved in the transport of
vesicles and organelles, or as
organelle tethers
Myosin V shows movement
similar to kinesin, with one head
bound to actin at all times
130. Unconvensional Myosins
Karp’s Cell & Molecular Biology (2020) Fig 9.47
Believed that long distance
transport occurs on
microtubules, with
microfilaments used for local
movement
132. Muscle
Organization
Karp’s Cell & Molecular Biology (2020) Fig 9.49
Skeletal muscle cell
(fiber) formed through
fusion of mononucleated
cells early in
development
Each myofibril is
composed of repeating
contractile units called
sarcomeres
133. Sarcomeres
Visible striations due to
the presence of thin and
thick filaments and their
regions of overlap
Z-lines are borders
between sarcomeres
Karp’s Cell & Molecular Biology (2020) Fig 9.49
136. Composition & Organization
Thin filaments are the microfilaments and associated
proteins
●
Tropomyosin fits within the goove of the microfilament,
7 actin subunits in length
●
Troponin globular protein which interacts with the end
of tropomyosin and with actin
Karp’s Cell & Molecular Biology (2020) Fig 9.52
137. Composition & Organization
Thick filaments are composed of several hundred myosin
molecules with bipolar orientation
Titin is an elastic protein stretching from M line to Z line
●
Maintains overall structure, aids relaxation
Karp’s Cell & Molecular Biology (2020) Fig 9.53
138. Molecular Basis of
Contraction
Each myosin filament head undergoes conformational
change to move actin filament 10 nm.
Each filament interacts with approx 100 myosin
molecules, resulting in continuous contraction of several
hundred nm
Karp’s Cell & Molecular Biology (2020) Fig 9.52
139. Swinging Lever Mechanism
1) Myosin tightly bound in absence of ATP
2) ATP binding results in release
3) ATP hydrolysis results in conformational change
4) Rebinding to actin 5) ADP realeased and repeat
http://www.esrf.fr/UsersAndScience/Publications/Highlights/2003/MX/MX03/
Lever arm
swings
140. Excitation-Contraction
Coupling
Transverse tubules
transmit impulses
from action
potentials to interior
of cell
Sarcoplamic
reticulum stores
calcium ions
needed to induce
muscle contraction
Karp’s Cell & Molecular Biology (2020) Fig 9.52
Muscle fibers organized into motor
units stimulated by a single nerve
143. Cellular Motility
Relies upon the presence of
actin networks in the cell
cortex (below the cell
membrane)
Processes include:
●
Endocytosis &
phagocytosis
●
Extension of processes
●
Cytokinesis
Organization/function
dependent on actin binding
proteins Karp’s Cell & Molecular Biology (2020) Fig 9.39
144. 1) Nucleating proteins
●
Spire contains multiple actin-binding domains to form
cluster for nucleation
●
Formins used to create and lengthen unbranched
filaments at the (+) end
●
Arp 2/3 complex is
template for addition
of actin monomers to
add branches
Actin Binding Proteins
Karp’s Cell & Molecular Biology (2020)
Fig 9.66
145. Actin Binding Proteins
Karp’s Cell & Molecular Biology (2020) Fig 9.60
2) Monomer-sequestering proteins (thymosins)
●
Bind actin-ATP monomers to prevent
polymerization
●
Regulates rate of polymerization/depolymerization
3) End-blocking (capping)
proteins
●
Prevent addition or loss
of actin
●
May be associated with
the (+) or (-) end
146. Actin Binding Proteins
4) Monomer polymerizing proteins
●
Profilin binds to same site as thymosin
●
Promotes removal of ADP, allowing ATP to bind
and polymerization to occur
5) Depolymerizing proteins (cofilin family)
●
Bind to pointed end to cause depolymerization
7) Filament-severing proteins
●
Cause fragmentation (eg. cofilin and gelsolin)
●
May create additional free barbed ends for growth,
or may act as capping proteins
147. Actin Binding Proteins
Karp’s Cell & Molecular Biology
(2020) Fig 9.60
6) Cross-linking and bundling
●
Flexible rod-like proteins
for forming mesh-like
network for support
(eg. filamin)
●
Globular bundling proteins
for parallel groupings
as seen in microvilli
(eg. villin & fimbrin)
8) Membrane-binding proteins
●
Anchorage for changes in
membrane shape
148. Cell Locomotion: “Crawling”
Karp’s Cell & Molecular Biology (2020) Fig 9.63
Protrusion formed
on leading edge
Lower surface of
protrusion attaches
to substratum
Majority of cell is
pulled forward
Rear contacts
broken
149. Lamellipodia
Karp’s Cell & Molecular Biology (2020) Fig 9.64
Dynamic fan-like or “ruffled”
protrusion on leading edge
of motile cells
150. Directed Motility
Karp’s Cell & Molecular Biology (2020) Fig 9.65
Stimulus results in activation of filament nucleating
proteins (Arp 2/3 complex) by WASP/WAVE
Polymerization of actin-ATP mediated by profilin
151. Directed Motility
Karp’s Cell & Molecular Biology (2020) Fig 9.65
Capping of older filaments occurs,
while allowing new branches to
continue growing, resulting in
the outgrowth of the
lamellipodium
152. Directed Motility
Karp’s Cell & Molecular Biology (2020) Fig 9.65
Older filaments are
comprised of actin-
ADP
Depolymerization of
the (-) ends of
capped
microfilaments
mediated by cofilin
Profilin allows
release of ADP to
allow formation of
actin-ATP for further
use
153. Traction Forces
Karp’s Cell & Molecular Biology (2020) Fig 9.65
Focal adhesions are
formed between the
leading edge of the
lamellipodium and
the substratum
These focal
adhesions allow for
the bulk of the cell to
be moved forward
by myosin and actin
Vinculin staining at
focal adhesions
154. Axonal Outgrowth
Karp’s Cell & Molecular Biology (2020) Fig 9.69
Growth cone at tip resembles a highly motile fibroblast
●
Broad lamellipodium
●
Short microspikes towards edge of lamellipodia
●
Elongated filipodia
Actin
Tubulin
155. Axonal Outgrowth
Karp’s Cell & Molecular Biology (2020) Fig 9.70
Direction of growth is determined by physical and chemical
stimuli detected by receptors in the growth cone
Tubulin Ephrin
f
●
Response to
chemoattractants
(eg. netrin) which
diffuse through
extracellular
environment
●
Interacting with
membrane-bound
molecules (eg. ephrin)
to encourage growth in
that particular direction.
156. Video 27:
Video 27:
Introduction to
Introduction to
Cell Signalling
Cell Signalling
https://www.kurzweilai.net/using-cells-chemical-signaling-to-control-cancer-or-detect-toxins
157. Cell Signalling &
Communication
Cells receive signals from the environment, which results
in a particular response:
●
Alterations in cell behavior (eg. Chemotaxis)
●
Alterations in gene expression (eg. Gene expression)
Multicellular organisms need to coordinate their behavior
●
Embryonic development
●
Cell division
158. Vocabulary
Signal molecules: extracellular molecules which act as
messengers between cells
Signalling cell: the cell which produces the signal molecule
Target cell: the cell receiving the signal
Receptor protein: a protein in the target cell which
recognizes and responds specifically to that signal
Signal transduction: means by which the message is
translated into a response
159. Receptors may be found
on the cell surface or
within the cell
Hydrophilic signals bind
to surface receptors
Hydrophobic signals
bind to intracellular
receptors
Receptor
Proteins
160. Autocrine Signalling
Receptors on the surface of the cell allow it to respond to a
signalling molecule it produces itself
Karp’s Cell & Molecular Biology (2020) Fig 15.1
161. Paracrine Signalling
Karp’s Cell & Molecular Biology (2020) Fig 15.1
Messenger produced by signalling cell acts on nearby
target cells: signal travels short distance through
extracellular space
Limited due to
their stability,
digestion by
enzymes, or
through
interactions
with the
extracellular
matrix
162. Endocrine Signalling
Karp’s Cell & Molecular Biology (2020) Fig 15.1
Messenger produced for long
distance signalling: signal
travels through bloodstream
Many hormones are
produced in organs distant
from the site of the target
cell
163. GAP JUNCTIONS
●
Hydrophilic channels
allow communication
between cells that form
during development
CNX OpenStax / Wikimedia Commons
Other Forms
of Cell
Signalling
https://projects.ncsu.edu/project/bio183de/
Lab/cells_celldivision/cells_celldivision1.html
SYNAPTIC
164. Signalling Overview
Karp’s Cell & Molecular Biology (2020) Fig 15.2
Diverse signalling molecules ranging from small soluble
compounds and proteins to large cell surface bound
glycoproteins
Specific receptors on
the target cell will bind
to their ligand
(signalling molecule)
165. Diversity of Extracellular
Messengers
Amino acids & their derivatives (eg. Epinephrine &
dopamine) act as neurotransmitters and hormones
Gases (NO, CO)
Cholesterol-derived steroid hormones
Eicosanoids (derived from fatty acids) act in regulating
various systemic responses (inflammation, blood
pressure)
Polypeptides/proteins on membrane of signalling cell or
secreted into extracellular environment
166. Cell Signalling Receptors
G protein-coupled receptors (GPCR): binding of ligand
results in activation of GTP-binding protein
Receptor protein-tyrosine kinases (RTK): binding of
ligand results in activation of kinase activity and
phosphorylation of target proteins
Ligand-gated channels: alterations in ion concentrations
lead to altered cellular activities (neurotransmission,
muscle contraction, calcium as a second messenger)
Steroid hormone receptors: intracellular, act as
transcription factors
167. Signalling Overview
Ligand binding to receptor results in conformational
change: transmits signal across membrane
Effector enzyme
generates small molecule
second messenger Karp’s Cell & Molecular Biology (2020) Fig 15.2
Recruitment of
signalling proteins
OR
169. The addition (kinases) or removal
(phosphatases) of phosphate
groups alter protein
conformation and
therefore activity
Termination of signalling
requires the destruction
or inactivation of
receptors, second
messengers, and
transduction proteins Karp’s Cell & Molecular Biology (2020) Fig 15.2
Signal Transduction
Pathways
Phosphorylation occurs
on serine, threonine
or tyrosine
Proteins are cytoplamic
or membrane-bound
171. Superfamily of receptors that mediate signalling through
interaction with G proteins
G Protein-Coupled
Receptors (GPCR)
Karp’s Cell & Molecular Biology (2020) Fig. 15.5
G proteins are
trimeric proteins that
bind to GDP/GTP
Following activation,
G proteins interact
with specific
effectors to initiate
signalling
172. Largest group of proteins in animals, with highly varied
roles in the cell
G Protein-Coupled
Receptors
Karp’s Cell & Molecular Biology (2020) Table 15.1
173. G Protein-Coupled Receptor
Action
Karp’s Cell & Molecular Biology (2020) Fig. 15.5
Consist of 7 a-helical
transmembrane
domains (also called
7TM receptors)
Extracellular loops form
binding site for ligand
Ligand binding will
results in
conformational change
in transmembrane
domains
N-term
C-term
174. G Protein-Coupled Receptor
Action
Karp’s Cell & Molecular Biology (2020) Fig. 15.5
Conformational change
results in strong affinity for
the G protein
Heterotrimeric G proteins
consist of three subunits:
●
a (contains GDP/GTP
binding site), b, and γ
●
Binding to receptor
results in exchange of
GDP for GTP
N-term
C-term
a
GDP/GTP
binding site
175. GPCR
Action
Karp’s Cell & Molecular Biology (2020) Fig. 15.6
GTP binding results in
dissociation of a from
b/γ and its interaction
with the effector
molecule to initiate the
signalling cascade
Hydrolysis of GTP to
GDP results in a
dissociation and the
effector being “turned
off”
176. GPCR Action
GDP-bound a loses affinity
for effector molecule and
associates with b/γ again
4 different types of G
proteins with different a
subunits which interact with
different effectors:
● Gs activate adenyl cyclase
● Gi inhibit adenyl cyclase
● Gq with phospholipase C b
(PLCb)
● G12/13 not characterized
Karp’s Cell & Molecular Biology (2020) Fig. 15.6
b/γ also involved in
signalling and interact
with adenyl cyclase
PLCb, and K+ and Ca2+
channels
177. Regulation of G Protein
Activity
G proteins with GTP bound interact with the effector
molecule to activate them
G proteins are slow-acting GTPases, resulting in their
eventual hydrolysis of bound GTP to GDP + Pi
Acceleration of this process occurs through the action of
regulators of G protein signaling (RGSs)
178. Termination of Response
●
G protein-coupled
receptor kinase (GRK)
are serine-threonine
kinases which
phosphorylate activated
GPCR
●
Phosporylated residues
are bound by arrestin,
which compete with G
proteins for binding to
GPCR Karp’s Cell & Molecular Biology (2020) Fig. 15.6
Effectors are no longer active after dissociation of the a
subunit, but the receptors need to undergo desensitization
in order to deactivate them:
179. Arrestin & Internalization
●
Inclusion in
signalling
complexes &
activation of
transcription
factors (3)
●
Digestion (4)
●
Recycled to
cell surface
(5/6)
Karp’s Cell & Molecular Biology (2020) Fig. 15.6
Arrestins associate with AP2 in clathrin-coated pits, which
results in GPCR accumulation within the pits
Endocytosis occurs, resulting in 3 potential roles:
180. GPCRs and Bacterial Toxins
Some bacterial toxins target the functioning of GPCRs
through targeting the function of the a subunits
●
Cholera toxin modifies a subunits by inhibiting GTPase
activity, leading to continual activation of adenylate
cyclase.
– This is the cause of diarrhea due to altered water
retention by intestinal cells.
●
Pertussis toxin inhibits function of a subunits, interfering
with signalling required for immune defense
182. Interact with multiple targets, resulting in a coordinated
rapid response to external stimuli
Most are soluble (except phosphoinositides & DAG) and
will rapidly diffuse through the cell
Include:
●
cyclic AMP/GMP (cAMP/cGMP)
●
phosphoinositides, diacylglycerol (DAG), inositol
triphosphate (IP3)
●
Ca2+
●
NO
Second Messengers
183. Cyclic AMP
Karp’s Cell & Molecular Biology (2020) Fig. 15.13
Production catalyzed by adenylyl cyclase
●
Interacts with GTP-bound G protein a
subunits
●
Recall that G proteins may either
activate adenylyl cyclase (as) or
inhibit its function (ai)
Each activated
adenylyl cyclase
allows a rapid
amplification of the
signal initiated through
ligand binding
184. Karp’s Cell & Molecular Biology (2020) Fig. 15.12
Reg
ulati
on
of
Bloo
d
Gluc
ose
In response to
glucagon (from
pancreatic a-cells)
or epinephrine
●
Through G protein-
coupled receptors
●
Also cause inhibition of
glycogen synthase
Activated by
insulin from
pancreatic b-cells
●
Mediated by a
receptor
protein-tyrosine
kinase
185. Glucose Mobilization
Karp’s Cell & Molecular Biology (2020) Fig. 15.14
2) Adenylyl cyclase in cell membrane
is activated & cAMP is produced
●
Downregulation may occur
through action of
phosphodiesterase
1) Ligand binding
results in G
protein activation
& mobilization of
the as subunit
3) cAMP then binds to &
activates protein kinase A
(PKA)
188. Glucose Mobilization
Karp’s Cell & Molecular Biology (2020) Fig. 15.14
9) PKA which enters the nucleus
phosphorylates the cAMP response
element-binding protein (CREB)
10) CREB binds response elements
within the promoter of genes to
upregulate their transcription
189. Regulation of PKA Targeting
PKA is known to
phosphoylate over 100
different substrates
Which responses occur
in a given cell type due
to:
●
Differential
expression of these
targets
●
Presence of PKA-
anchoring proteins
(AKAPs)
Karp’s Cell & Molecular Biology (2020) Fig. 15.15
190. Regulation of PKA Targeting
Different AKAPs found within specific membranes in
different cell types
Karp’s Cell & Molecular Biology (2020) Fig. 15.16
Sequester PKAs to certain cellular
regions to coordinate their
interactions with targets
191. Phosphatidylinositol (PI)
Numerous lipid derivatives function as second messengers
Enzymatically altered by phospholipases, phospholipid
kinases, and phospholipid phosphatases
Those derived from PI called phosphoinositides
Hbf878, CC0, via Wikimedia Commons
192. Phosphoinositides
Number of derivatives are created through the actions of
kinases which remain associated with the membrane
PI(4)P, PI(4,5)P2, and PIP3 (not shown) all act though
interaction of the phosphorylated inositol ring with lipid-
binding domain containing proteins
Karp’s Cell & Molecular Biology (2020) Fig. 15.10
Domain acts
to recruit
these
proteins to
the membrane
for protein-
protein
interactions
193. Phospholipase C (PLC)
Karp’s Cell & Molecular Biology (2020) Fig. 15.10
GPCR binding may also lead to
activation of phosphatidylinositol-
specific phospholipase C-b, which
cleaves PI(4,5)P2
Diacylglycerol
Inositol 1,4,5-
triphosphate
194. Diacylglycerol (DAG)
https://www.mdpi.com/2072-6694/6/2/860
DAG remains associated with the membrane and binds to
proteins containing the DAG-binding domain
Protein kinase C (PKC) associates with DAG and
phosphorylates various targets:
●
Extracellular
signal molecule
release
●
Cell growth &
differentiation
●
Metabolism
●
Apoptosis
●
Immunity
195. Inositol 1,4,5-triphosphate
Karp’s Cell & Molecular Biology (2020) Fig. 15.10
IP3
is a soluble second messenger which will rapidly
diffuse through the cell
IP3
receptor on SER is a calcium channel, which opens
upon binding
Ca2+
also a second
messenger,
interacting with
various targets:
●
Muscle
contraction
●
Exocytosis
●
Cell shape
197. Receptor Protein-Tyrosine
Kinases
Large number of kinases expressed by different cell types
Approximately 2/3 of tyrosine kinases are membrane-
bound receptors which are activated through ligand
binding and dimerization
●
Ligands inclued growth factors & hormones
Regulate diverse processes:
●
Cell growth & proliferation
●
Differentiation
●
Cellular motility
199. Receptor Protein-Tyrosine
Kinases
Karp’s Cell & Molecular Biology (2020) Fig. 15.17
In the absence of
phosphorylation, the
ATP-binding active site
of the kinase domain is
blocked by the
activation loop
Phosphorylation results
in activation loop being
in stable conformation
away from the active
site, allowing trans-
autophosphorylation of
adjacent cytoplasmic
domains
200. Receptor Protein-Tyrosine
Kinases
Karp’s Cell & Molecular Biology (2020) Fig. 15.17
The phosphorylated
tyrosines and their
surrounding amino acid
sequences determine
the specificity of
interactions with
signalling proteins
Most characterized
domains:
●
Src-homology 2
(SH2)
●
Phosphotyrosine-
binding (PTB)
201. RTK Signal
Transduction
Karp’s Cell & Molecular Biology (2020) Fig. 15.19
May be bound by adaptor
or scaffolding proteins
which allow the
recruitment of other
proteins
Docking proteins may
themselves be
phosphorylated by the
receptor to allow
interaction with signalling
molecules
202. RTK Signal Transduction
Karp’s Cell & Molecular Biology (2020) Fig. 15.19
Many transcription
factors are able to bind
to activated RTKs
Binding results in
phosphorylation, leading
to dimerization
Following dimerization,
the transcription factor is
transported into the
nucleus, where it binds
specific DNA sequences
to allow transcription
203. RTK Signal Transduction
Karp’s Cell & Molecular Biology (2020) Fig. 15.19
Activation of enzymes
through:
●
Recruitment to membrane
& co-localization with
substrate
●
Conformational change
due to binding to receptor
●
Phosphorylation
Regulation of enzymatic activity by RTKs is also common
●
Kinases, phosphatases, lipases
204. Turning RTK Signals Off
Karp’s Cell & Molecular Biology (2020) Fig. 8.42
Ubiquitin ligases contain
SH2 domains which allow
them to associate with
RTKs and label them for
internalization
Ubiquitination results in
interaction with the AP2
adaptor which localizes
the receptors into clathrin-
coated pits for endocytosis
●
Destruction in the lysosome
●
Recycling back to cell surface
●
Use in endosomes for
intracellular signalling
205. Signalling
Cascades
Karp’s Cell & Molecular Biology (2020) Fig. 15.22
Most well known RTK pathway is
the Ras-MAP kinase pathway:
●
Activation of Ras (a small G
protein) through GTP binding
●
Sequential activation of protein
kinases
●
Phosphorylation of targets
including transcription factors,
other kinases, cytoskeletal
components, and more
206. https://erc.bioscientifica.com/view/journals/erc/26/6/ERC-19-0098.xml
Small G Proteins
Monomeric G proteins, similar in function to the
heterotrimeric G proteins (see GPCRs)
●
Interaction with adaptor (Grb2/Sos) makes nucleotide
binding site of Ras available
●
Ras active when GTP is bound
●
GTPase function, resulting in
hydrolysis to GDP and inactivity
Ras functions by recruiting
Raf to the membrane,
leading to its phosphoryation
and activation
207. Karp’s Cell & Molecular Biology (2020) Fig. 15.21
Regulation of
Small G Proteins
3 types of accessory proteins are
involved in the regulation of small G
proteins
1) Guanine nucleotide
dissociation inhibitors (GDIs)
●
Prevent the release of GDP
●
Results in maintenance of
inactive G proteins
208. Karp’s Cell & Molecular Biology (2020) Fig. 15.21
Regulation of
Small G Proteins
2) Guanine nucleotide-exchange factors
(GEFs)
●
Binding allows the exchange of GDP for
GTP, resulting in activation of the G
protein
●
Binding of the G protein to its target
results in GEF release, activation of
the target & signal transduction
209. Karp’s Cell & Molecular Biology (2020) Fig. 15.21
Regulation of
Small G Proteins
3) GTPase-activating proteins (GAPs)
●
Binding to G protein/target complex results in
acceleration of GTPase activity
●
Once GTP hydrolysis occurs,
complex disassociates
210. Regulation of MAP Kinase
Pathways
Scaffolding proteins
allow specific
assembly of
components for
mediating particular
processes
Kinases only
phosphorylate specific
substrates
Inactivation of MAP
kinases by
phosphatases (MKP) https://erc.bioscientifica.com/view/journals/erc/26/6/ERC-
19-0098.xml
211. Karp’s Cell & Molecular Biology (2020) Fig. 15.12
Reg
ulati
on
of
Bloo
d
Gluc
ose
In response to
glucagon (from
pancreatic a-cells)
or epinephrine
●
Through G protein-
coupled receptors
●
Also cause inhibition of
glycogen synthase
Activated by
insulin from
pancreatic b-cells
●
Mediated by a
receptor
protein-tyrosine
kinase
212. a and b chains
produced from single
polypeptide
a chain contains the
insulin binding domain
b chain is
transmembrane protein
with tyrosine kinase
domain
Exists as stable dimer
even in the absence of
insulin
Insulin binding causes
confromational change
in kinase domains
Karp’s Cell & Molecular Biology (2020) Fig. 15.24
Insulin Receptor
213. Autophosphorylaed insulin receptor binds to
PTB domain of insulin receptor sustrates (IRS-1
& IRS-2)
IRSs also have PH domain (interact with
phospholipids on membrane)
Phosphorylated tyrosines interact with signal
molecules with SH domains
Karp’s Cell & Molecular Biology (2020) Fig. 15.24
Insulin Receptor
214. Following activation by binding to IRS, PI3K produces
phosphoinositide PIP3 which leads to the recruitment of PKB
& PDK1
Karp’s Cell & Molecular Biology (2020) Fig. 15.24
Role of PI 3-kinase
PDK1 &
mTOR
activate PKB
for signal
transduction
PKB mediates
glucose uptake by
causing fusion of
GLUT4 receptor
vesicles with
membranes
216. Karp’s Cell and Molecular Biology (2020) Fig 4.56
Calcium plays important
roles in cell functions
●
Synaptic
transmission
●
Muscle
contraction
https://schoolbag.info/biology/mcat/53.html
Calcium as an Intracellular
Messenger
217. Inositol 1,4,5-triphosphate &
Calcium
Karp’s Cell & Molecular Biology (2020) Fig. 15.10
IP3
receptor on SER
is a calcium channel,
which opens upon
binding
GPCR binding may
also lead to activation
of Phospholipase C-
b, which cleaves PIP2
to produce DAG and
IP3
Cytoplasmic calcium concentration normally low (10-7
M)
218. IP3-mediated signalling
due to oscillation in
cytoplasmic calcium
levels
IP3
and Calcium Oscillation
Karp’s Cell & Molecular Biology (2020) Fig. 15.11 & Table 15.2
219. Opening of voltage-gated Ca2+
channels (1) leads to entry of
some Ca2+ ions
Binds to ryanodine receptors
(RyR) (2) on the surface of the
SER
Triggers opening of these
channels and release of stored
Ca2+ from ER (3)
Karp’s Cell & Molecular Biology (2020) Fig. 15.28
Calcium-induced
Calcium
Release
220. Cytoplasmic concentration restored
through action of:
●
Ca2+ pumps in ER (4)
●
Na+/Ca2+ exchanger in plasma
membrane (5)
Response may be localized in small
region or may result in increasing,
spreading wave throughout cell
Karp’s Cell & Molecular Biology (2020) Fig. 15.28
Calcium-induced
Calcium
Release
221. Sperm contain a phospholipase, which cleave PIP2
contained within the egg to produce PI3
Karp’s Cell & Molecular Biology (2020) Fig. 15.29
Calcium wave in Fertilization
PI3 binds
receptors on
the SER,
resulting in
calcium wave
Image
produced here
every 10
seconds
222. Karp’s Cell & Molecular Biology (2020) Fig. 15.30
Store-Operated Calcium
Entry
STIM1 are calcium-sensing proteins which are normally
dispersed throughout the ER membrane
223. Karp’s Cell & Molecular Biology (2020) Fig. 15.30
Store-Operated Calcium
Entry
STIM1 become clustered
near plasma membrane &
recruit Orai1
Cellular stores may become depleted
through repeated responses
Orai1 Ca2+ ion
channels allow
import of Ca2+ &
storage in ER
224. Cell-type specificity due to
ability to:
●
Activate/inhibit enzymes
●
Alter transport
●
Change membrane
permeability
●
Cause membrane fusion
●
Impact structure and
function of the cytoskeleton
Cellular
Effects of Ca2+
225. Mediate effects of calcium through
interacting with it and target proteins
Calmodulin most widely studied and found in
all eukaryotes
●
Low affinity for calcium, so only binds
when calcium increased in cytoplasm
●
Alters conformation and binds to cell-
specific targets
●
Targets include the Na+/Ca2+ exchanger,
thereby acting to bring a halt to further
signalling as well.
Calcium-binding Proteins
Karp’s Cell & Molecular Biology (2020) Fig. 15.31
226. Karp’s Cell and Molecular Biology (2020) Fig 15.33
Nitric Oxide
Acts as both an extracellular and a
second messenger to regulate
various processes
Acetylcholine signalling (1) results
in the influx of Ca2+ (2),
which activates nitric
oxide synthase (NOS)
NOS produces NO
from arginine (3), &
NO diffuses from the
endothelial cell into
neighbouring smooth
muscle cells (4)
227. Karp’s Cell and Molecular Biology (2020) Fig 15.33
Nitric Oxide
In the muscle cell, NO binds and
activates guanylyl cyclase, which
produces cGMP (5)
cGMP is a second messenger,
which mediates muscle
relaxation through the
activation of a cGMP-
dependent protein
kinase, which results
in blood vessel
dilation
Nitroglycerine is
treatment for angina:
catabolized to NO
Converted to
GTP by cGMP
phosphodiesterase
228. Multiple different ligands can
result in the activation of a single
effector = convergence
Convergence, Divergence &
Crosstalk
eg. Both GPCR & TKR
activate PLCs
Karp’s Cell and Molecular Biology (2020) Fig 15.33
229. Signals from the same ligand
can result in the activation of
more than one effector =
divergence
Convergence, Divergence &
Crosstalk
eg. PLC, PI3K, & GAP all
activated by TKR
Karp’s Cell and Molecular Biology (2020) Fig 15.33
230. Different pathways may
regulate each other = crosstalk
Convergence, Divergence &
Crosstalk
eg. Calcium can inhibit
PKC activity
Karp’s Cell and Molecular Biology (2020) Fig 15.33
232. Karp’s Cell and Molecular Biology (2020) Fig 15.37
Apoptosis
(Programmed Cell Death)
Ordered destruction of the cell which is essential in the
process of development and maintenance of health in
multi-cellular organisms
234. Apoptosis vs Necroptosis
Apoptosis results in safe
clearance of cellular
components
Karp’s Cell and Molecular Biology (2020) Fig 15.37
Rupturing of cellular
membranes during
necroptosis results in
release of cellular
components, resulting in
inflammation
https://www.creative-diagnostics.com/
necroptosis-signaling-pathway.htm
235. Karp’s Cell and Molecular Biology (2020) Fig 15.38
Apoptosis in Development
Cells which are located between the eventual digits
undergo apoptosis, with macrophages (blue fluorescence)
ingesting the apoptotic bodies.
236. Apoptosis in Maintaining
Health
●
Prevention of autoimmunity: eliminate T cells and B cells
with interact with “self” antigens.
●
Down-regulation of immunity following clearance of
pathogens.
●
Removal of cells with irreparable DNA damage
– Loss of appropriate triggering of apoptosis is a central
feature of cancerous cells
●
Inappropriate triggering of apoptosis leads to disease
(eg. neurodegeneration)
237. Intrinsic Pathway
Regulated by members of the Bcl-2 family of mitochondrial
proteins upon receiving internal stimuli
●
Both pro-apoptotic and anti-apoptotic members with
several BH domains are normally expressed and
associate with one another in the membrane
●
Proapoptotic BH3-only members act as initiators of
apoptosis by inhibiting the anti-apoptotic members and
activating the proapoptotic members
●
Following activation, pro-apoptotic Bax/Bak form pores in
the mitochondrial outer membrane, allowing the release
of cytochrome c (& other mediators) from the
intermembrane space
238. Karp’s Cell and Molecular Biology (2020) Fig 15.40
Intrinsic Pathway
Cytochrome c then interacts
with various cytoplamic proteins
and procaspase-9
This is the activated initiator or
apoptosome
Caspase-9 cleaves numerous
other “executioner”
procaspases, leading to their
activation
239. Caspases
Family of cysteine proteases which are central in the
activation of cell death pathways.
Targets are varied cellular components including:
●
Proteins regulating cell adhesion: isolates cell from its
neighbours
●
Proteins involved in regulating anti-apoptotic signal
pathways
●
Cytoskeletal proteins, including the lamins
●
Inhibitors of DNA digestion: initiates the destruction of
the genome
240. Karp’s Cell and Molecular Biology (2020) Fig 15.39
Extrinsic Pathways
Tumor-necrosis factor (TNF) is a
cytokine produced in response
to infection by intracellular
pathogens and other
environmental stresses.
Following activation, the TNF
receptor death domains bind to
an adaptor protein (TRADD) for
the recruitment of effector
proteins (RIP1K).
Signalling results in apoptosis,
necroptosis, or cell survival?
241. Karp’s Cell and Molecular Biology (2020) Fig 15.39
Extrinsic Pathways:
Apoptosis
RIP1K can associate with
FADD to recruit 2 molecules of
procaspase-8
Procaspases cleave each
other to produce activated
caspase-8
Caspase-8 acts of various
“executioner” procaspases to
activate them and initiate the
apoptotic pathway
242. Karp’s Cell and Molecular Biology (2020) Fig 15.39
Extrinsic Pathways:
Necroptosis
Much less understood then
apoptotic pathway
Association of RIP1K with
RIP3K leads to their
phosporylation and formation
of the necrosome
Phosphorylation of MLKL and
its insertion in the membrane
interferes with phospholipid
structure and membrane
stability
243. Extrinsic Pathways:
Cell Survival?
TNF binding to the TNFR also results in activation of the NF-kB
transcription factor
●
First identified in B cells, but utilized in all animal cells as a
positive regulator for cell survival and proliferation
●
Normally sequestered in cytoplasm through association with
IkBs (inhibitor proteins), which become phosphorylated
following TNF binding and inactivated
●
Following release, NF-kB relocates to the nucleus to initiate
transcription.
●
Inappropriate expression linked to the development of
cancer