This presentation gives an overview of Lipid Rafts, how it was discovered, its importance and the future research in this area,Feel free to comment and ask any questions
This presentation gives an overview of Lipid Rafts, how it was discovered, its importance and the future research in this area,Feel free to comment and ask any questions
The delivery of newly synthesized protein to their proper cellular destination, usually referred to as protein targeting or sorting.
The mode of protein transport depends chiefly on the location in the cell cytoplasm of the polysomes involved in protein synthesis.
There are two modes of protein sorting:-
1) Co - translational Transportation.
2) Post - translational Transportation.
ultra structure of Ribosome, Prokaryotic Ribosome, Eukaryotic Ribosome, Svedberg unit, Centrifugal force, assembly of Ribosome, functions of Ribosome, models of Ribosomes, fine structure of Ribosome, Discovery of Ribosome,
Describes the plasma membrane in detail, explains the each major component with its functions.
Transport mechanism across the cell is covered with detailed explanation with examples.
by Dr. N.Sivaranjani, MD
I have tried to make a precise presentation on protein transport, targeting and sorting into organelle's other than nucleus. Hope this might help you. Comments are welcome.
Details of cytoskeleton element-microtubule. The Microtubule associated protein-type and function, Treadmilling and dynamic instability, Structure of cilia and flagella
Structure and functions of endoplasmic reticulumICHHA PURAK
The presentation consists of 57 slides,describes following heads
• DISCOVERY
• INTRODUCTION
• BIOGENESIS OF ER
• ISOLATION OF MICROSOMES FROM E R
• STRUCTURE
• COMPONENTS OF ER
CISTERNAE
VESICLES
TUBULES
• MAIN FUNCTION OF ER
• TYPES OF ENDOPLASMIC RETICULUM
• SMOOTH ENDOPLASMIC RETICULUM (SER)
• FUNCTIONS OF SER
• ROUGH ENDOPLASMIC RETICULUM (RER)
• FUNCTIONS OF RER
• SUMMARY
• REFERENCES
• QUESTIONS
The delivery of newly synthesized protein to their proper cellular destination, usually referred to as protein targeting or sorting.
The mode of protein transport depends chiefly on the location in the cell cytoplasm of the polysomes involved in protein synthesis.
There are two modes of protein sorting:-
1) Co - translational Transportation.
2) Post - translational Transportation.
ultra structure of Ribosome, Prokaryotic Ribosome, Eukaryotic Ribosome, Svedberg unit, Centrifugal force, assembly of Ribosome, functions of Ribosome, models of Ribosomes, fine structure of Ribosome, Discovery of Ribosome,
Describes the plasma membrane in detail, explains the each major component with its functions.
Transport mechanism across the cell is covered with detailed explanation with examples.
by Dr. N.Sivaranjani, MD
I have tried to make a precise presentation on protein transport, targeting and sorting into organelle's other than nucleus. Hope this might help you. Comments are welcome.
Details of cytoskeleton element-microtubule. The Microtubule associated protein-type and function, Treadmilling and dynamic instability, Structure of cilia and flagella
Structure and functions of endoplasmic reticulumICHHA PURAK
The presentation consists of 57 slides,describes following heads
• DISCOVERY
• INTRODUCTION
• BIOGENESIS OF ER
• ISOLATION OF MICROSOMES FROM E R
• STRUCTURE
• COMPONENTS OF ER
CISTERNAE
VESICLES
TUBULES
• MAIN FUNCTION OF ER
• TYPES OF ENDOPLASMIC RETICULUM
• SMOOTH ENDOPLASMIC RETICULUM (SER)
• FUNCTIONS OF SER
• ROUGH ENDOPLASMIC RETICULUM (RER)
• FUNCTIONS OF RER
• SUMMARY
• REFERENCES
• QUESTIONS
Explain the “life” of a secreted protein molecule - trace the pathwa.pdfArrowdeepak
Explain the “life” of a secreted protein molecule - trace the pathway in a cell by which a secreted
protein, such as an antibody, would be produced in an animal cell, starting in the nucleus.
Solution
Cells secrete proteins for their own cytosol or for release into surrounding extracellular fluid.
These secretions may include various hormones, digestive enzymes, antibodies, mucus etc.
The transcription process (conversion of DNA to mRNA) occurs inside the nucleus. This newly
formed mRNA is translated into proteins in the cytosol at cellular structures called ribosomes.the
ribosome remains in the cytosol if the protein has to be used within the cell, whereas if it is
destined for secretion outside the cell, the signal sequence (first few amino acids) is synthesized
on the ribosome and then the ribosome docks at the rough endoplasmic reticulum (RER) for
completion of protein synthesis. Proteins enter and cross endoplasmic recticulum (ER)
membrane co-translationally (i.e., they cross ER during synthesis of polypeptide). In the lumen
of ER, proteins undergo glycosylation and molecular chaperones aid in the process of protein
folding. Misfolded proteins are retrotranslocated to the cytosol, where they are degraded by a
proteasome action.
The vesicles with correctly folded proteins then enter the golgi appratus where further
posttranslational modifications occur including cleavage and functionalization. When the protein
moves through the entire Golgi apparatus, it buds off as secretion vesicles. Now, with the help of
cell\'s cytoskeleton, it moves towards the edge of the cell and attaches itself to the membrane.
Eventually, vesicle fuses with the cell membrane releasing its contents out of the cell through
the process of exocytosis.
This secretion pathway is followed for all protein molecules including antibodies..
The endoplasmic reticulum is a very important part of the eukaryotic cell. It is a network of membranes that performs different functions depending on its type and location. There are two types of endoplasmic reticulum: rough and smooth. The rough endoplasmic reticulum has ribosomes attached to it, which are the sites of protein synthesis. The smooth endoplasmic reticulum does not have ribosomes, but it is involved in lipid synthesis, hormone production, and detoxification. The endoplasmic reticulum is connected to the nuclear membrane and the Golgi apparatus, and it helps transport proteins and lipids within the cell
1)calcium(pH-dependent regulation of lysosomal calcium in macrophage.pdfravikapoorindia
1)calcium(pH-dependent regulation of lysosomal calcium in macrophages)
Pulmonary macrophages are motile cells that respond to contact with suitable surfaces or
micron-sized objects by undergoing movements that lead to spreading and phagocytosis. There is
evidence that interactions of actin and other proteins in the cortical cytoplasm of macrophages
provide the motor power for these movements and that variations in free calcium concentrations
in the cortical cytoplasm of macrophages might control their directionality (1). If the plasma
membrane maintains a large electrochemical gradient of calcium between the extracellular
environment and the cytoplasm, a slight alteration of its activity could result in a considerable
variation of cytoplasmic free calcium concentrations. If contact of the external surface of the
plasma membrane with certain surfaces were somehow coupled to the calcium gradient-
maintaining activity of the membrane, the interaction could lead to changes in peripheral
cytoplasmic calcium levels. We have studied calcium transport across the macrophage plasma
membrane, using phagocytic vesicles. Phagocvtic vesicles arise from the internalization of
plasma membrane and thus constitute a system to study easily its inner surface. Furthermore,
when prepared from macrophages that have ingested oil droplets, they can be purified rapidly by
flotation with good yield and in an intact state (2). Using this approach, we have characterized a
high affinity MgATP-dependent calcium pump located in the inner side of the plasma membrane
2).the protein was translated using ribosomes inside the ER(
The endomembrane system (endo- = “within”) is a group of membranes and organelles in
eukaryotic cells that works together to modify, package, and transport lipids and proteins. It
includes a variety of organelles, such as the nuclear envelope and lysosomes, which you may
already know, and the endoplasmic reticulum and Golgi apparatus, which we will cover shortly.
Although it\'s not technically inside the cell, the plasma membrane is also part of the
endomembrane system. As we\'ll see, the plasma membrane interacts with the other
endomembrane organelles, and it\'s the site where secreted proteins (like the pancreatic enzymes
in the intro) are exported. Important note: the endomembrane system does not include
mitochondria, chloroplasts, or peroxisomes.
Let\'s take a closer look at the different parts of the endomembrane system and how they
function in the shipping of proteins and lipids.
The endoplasmic reticulum
The endoplasmic reticulum (ER) plays a key role in the modification of proteins and the
synthesis of lipids. It consists of a network of membranous tubules and flattened sacs. The discs
and tubules of the ER are hollow, and the space inside is called the lumen.
Rough ER
The rough endoplasmic reticulum (rough ER) gets its name from the bumpy ribosomes attached
to its cytoplasmic surface. As these ribosomes make proteins, they feed the newly formin.
Animal cells are eukaryotic cells or cells with a membrane-bound nucleus.
DNA in animal cells is housed within the nucleus.
In addition to having nucleus animal cells also contain other membrane-bound organelles.
Organelles have a wide range of responsibilities that include everything from producing hormones and enzymes to providing energy for animal cells.
All living things are made up of cells that make up their body structure. Some of these living things are single-celled and other organisms are made up of more than one cell.
This is the first one of a series of lectures about the "Cell". I am here introducing some basic principles about the cell structure, types, histology and biochemistry
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...
Role of endoplasmic reticulum in protein systhesis and1
1. ROLE OF ENDOPLASMIC RETICULUMIN PROTEIN
SYSTHESIS AND TRANSPORT
TO BE PRESENTED BY:
MONALISA BEHERA
M.Sc. (PREVIOUS)
DEPT. OF GENETICS AND PLANT
BREEDING
2. INTRODUCTION:
Cell is the structural and functional unit of all living organisms,
except viruses. Various structures are visible in a cell, under a
light microscope and some other electron microscope. Some of
the structures are ;
Cell wall
Plasma lemma or cell membrane
Endoplasmic reticulum
Ribosomes
Mitochondria etc.,
Out of these organelles endoplasmic reticulum is a type
of organelle present in the cells of eukaryotic organisms that
forms an interconnected network of flattened, membrane-
enclosed sacs or tubes known cisternae.
3. The membranes of the ER are continuous with the outer
membrane of the nuclear envelope.
Endoplasmic reticulum occurs in most types of eukaryotic
cells, including the most primitive Giardia,[1] but is absent
from Red blood cells and spermatozoa.
The primary function of the smooth ER is to serve as a
platform for the synthesis of lipids (fats), carbohydrate
(sugars) metabolism , and the detoxification of drugs and
other toxins.
Tissues and organs that directly participate in these activities,
such as the liver, are enriched in smooth ER.
4. Morphologically, the rough ER is studded with ribosomes that
participate in protein synthesis giving its "rough" appearance
when viewed with the electron microscope.
The proteins synthesized on the ER are transported from the ER
membranes by small vesicles that pinch off the surface and
enter the Golgi membrane stack (cisternae). From the Golgi, the
proteins are transported to the cell surface or to
other organelles .
5. ENDOPLASMICRETICULUM: AN OVERVIEW
The endoplasmic reticulum (ER) is a network of membrane-
enclosed tubules and sacs (cisternae) that extends from the
nuclear membrane throughout the cytoplasm.
The entire endoplasmic reticulum is enclosed by a continuous
membrane and is the largest organelle of most eukaryotic
cells.
Its membrane may account for about half of all cell
membranes, and the space enclosed by the ER (the lumen, or
cisternal space) may represent about 10% of the total cell
volume.
6.
7. There are two distinct types of ER that perform different
functions within the cell;
1. Smooth endoplasmic reticulum
2. Rough endoplasmic reticulum
The rough ER, which is covered by ribosomes on its outer
surface, functions in protein processing. The smooth ER is
not associated with ribosomes and is involved in lipid, rather
than protein, metabolism.
Rough ER is mainly composed of cisterns and is found in
cells actively involved in protein synthesis. Smooth and
Rough ER change into each other as per the needs of a cell.
8.
9. ENDOPLASMIC RETICULUM IN PROTEIN
SYNTHESIS:-
The binding site of the ribosome on the RER is the translocon.
[The translocon (commonly known as a translocator or translocation
channel) is a complex of proteins associated with the translocation of
polypeptides across membranes.]
The role of the endoplasmic reticulum in protein processing and
sorting was first demonstrated by George Palade and his
colleagues in 1960s.
However, the ribosomes bound to ER at any one time are not a stable
part of this organelle's structure as they are constantly being bound and
released from the membrane.
A ribosome only binds to the RER once a specific protein-nucleic acid
complex forms in the cytosol.
10. This special complex forms when a free ribosome begins translating
the mRNA of a protein destined for the secretory pathway.
The first 5-30 amino acids polymerized encode a signal peptide, a
molecular message that is recognized and bound by a signal
recognition particle (SRP).
[The SRP is a small protein/RNA complex that acts as a targeting guide
and is essential for protein translocation into the rER lumen (interior
chamber)].
Translation pauses and the ribosome complex binds to the
RER translocon where translation continues with the nascent protein
forming into the RER lumen and/or membrane.
The protein is processed in the ER lumen by an enzyme (a
signal peptidase), which removes the signal peptide.
11.
12.
13.
14.
15. Many proteins in yeast, as well as a few proteins in mammalian
cells, are targeted to the ER after their translation is complete
(posttranslational translocation), rather than being transferred into
the ER during synthesis on membrane-bound ribosomes.
These proteins are synthesized on free cytosolic ribosomes, and
their posttranslational incorporation into the ER does not
require SRP.
Instead, their signal sequences are recognized by distinct receptor
proteins (the Sec62/63 complex) associated with the Sec61
complex in the ER membrane .
16. Cytosolic chaperones are required to maintain
the polypeptide chains in an unfolded conformation so they can
enter the Sec61 channel, and another chaperone within the ER
(called BiP) is required to pull the polypeptide chain through
the channel and into the ER.
The translocon complex consists of several large protein
complexes. The central element is the translocation channel
itself, the heterotrimer Sec61.
17.
18.
19. PROTEIN FOLDING:-
The ER lumen maintains a chemical environment that ensures
that proteins are folded into the correct conformation .
(Misfolded proteins are useless and may cause problems if
they are detected as "foreign structures" by the immune
system of the body).
Newly synthesized proteins are quickly associated with ER
"chaperone proteins" and folding enzymes that assist in the
folding of the proteins into their correct conformations.
For example, one of the major proteins within the ER lumen is a
member of the Hsp70 family of chaperones called BiP(Binding
immunoglobulin protein).
20. BiP is thought to bind to the unfolded polypeptide chain as it crosses the
membrane and then mediates protein folding and the assembly of
multisubunit proteins within the ER .
Correctly assembled proteins are released from BiP and are
available for transport to the Golgi apparatus.
Abnormally folded or improperly assembled proteins, however,
remain bound to BiP and are consequently retained within the
ER or degraded, rather than being transported farther along the
secretory pathway.
It is not known exactly how the ER recognizes misfolded
proteins, but it may be able to recognize specific domains or
segments on the proteins.
For example, a hydrophobic domain (water-avoiding segment)
should be tucked away inside the protein, but a misfolded protein
may have this domain protruding outward. Such a protein would be
retained and degraded.
21.
22. PROTEIN TRANSPORT
Newly synthesized proteins enter the biosynthetic- secretory
pathway in the ER by crossing the ER membrane from
the cytosol.
During their subsequent transport, from the ER to the Golgi
apparatus and from the Golgi apparatus to the cell surface and
elsewhere, these proteins pass through a series of compartments,
where they are successively modified.
Transfer from one compartment to the next involves a delicate
balance between forward and backward (retrieval) transport
pathways. Some transport vesicles select cargo molecules and
move them to the next compartment in the pathway, while others
retrieve escaped proteins and return them to a previous
compartment where they normally function.
23.
24. Thus, the pathway from the ER to the cell surface involves many
sorting steps, which continually select membrane and soluble
lumenal proteins for packaging and transport—in vesicles
or organelle fragments that bud from the ER and Golgi apparatus.
To initiate their journey along the biosynthetic-secretory pathway,
proteins that have entered the ER and are destined for the Golgi
apparatus or beyond are first packaged into small COPII-coated
transport vesicles.
These transport vesicles bud from specialized regions of the ER
called ER exit sites, whose membrane lacks bound ribosomes. In
most animal cells, ER exit sites seem to be randomly dispersed
throughout the ER network.
25. After transport vesicles have budded from an ER exit site and
have shed their coat, they begin to fuse with one another.
This fusion of membranes from the same compartment is
called homotypic fusion, to distinguish it from heterotypic
fusion, in which a membrane from one compartment fuses with
the membrane of a different compartment.
As with heterotypic fusion, homotypic fusion requires a set of
matching SNAREs.
[SNARE proteins (an acronym derived from "SNAP
(Soluble NSF Attachment Protein) Receptor") are a large protein
superfamily consisting of more than 60 members in yeast and
mammalian cells.[1] The primary role of SNARE proteins is to
mediate vesicle fusion, that is, the fusion of vesicles with their
target membrane bound compartments].
26. In this case, however, the interaction is symmetrical, with v-
SNAREs and t-SNAREs contributed by both membranes.
SNAREs can be divided into two categories: vesicle or v-SNAREs,
which are incorporated into the membranes of transport vesicles
during budding, and target or t-SNAREs, which are located in the
membranes of target compartments.
27.
28.
29. These clusters constitute a new compartment that is separate
from the ER and lacks many of the proteins that function in the
ER.
They are generated continually and function as transport
packages that bring material from the ER to the Golgi apparatus.
The clusters are relatively short-lived because they quickly
move along microtubules to the Golgi apparatus, where they
fuse and deliver their contents.
As soon as vesicular tubular clusters form, they begin budding
off vesicles of their own. Unlike the COPII-coated vesicles that
bud from the ER, these vesicles are COPI-coated. They carry
back to the ER resident proteins that have escaped, as well as
proteins that participated in the ER budding reaction and are
being returned.
30.
31. The retrieval (or retrograde) transport continues as the vesicular
tubular clusters move to the Golgi apparatus. Thus, the clusters
continuously mature, gradually changing their composition as
selected proteins are returned to the ER.
A similar retrieval process continues from the Golgi apparatus,
after the vesicular tubular clusters have delivered their cargo.
32. REFERENCE
Soltys, B.J., Falah, M.S. and Gupta, R.S. (1996) Identification
of endoplasmic reticulum in the primitive eukaryote Giardia
lamblia using cryoelectron microscopy and antibody to Bip. J.
Cell Science 109: 1909-1917.
Levine T (September 2004). "Short-range intracellular
trafficking of small molecules across endoplasmic reticulum
junctions". Trends Cell Biol. 14 (9): 483–90
Endoplasmic reticulum. (n.d.). McGraw-Hill Encyclopedia of
Science and Technology. Retrieved September 13, 2006, from
Answers.com
Web site:http://www.answers.com/topic/endoplasmic-reticulum