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BIOLOGY Campbell ā€¢ Reece ā€¢ Urry ā€¢ Cain ā€¢ Wasserman ā€¢ Minorsky ā€¢ Jackson Ā© 2015 Pearson Education Ltd TENTH EDITION Global Edition Lecture Presentation by Nicole Tunbridge and Kathleen Fitzpatrick 9 Cellular Signaling
Ā© 2015 Pearson Education Ltd Cellular Messaging a) Cells can signal to each other and interpret the signals they receive from other cells and the environment b) Signals are most often chemicals c) The same small set of cell signaling mechanisms shows up in diverse species and processes
Ā© 2015 Pearson Education Ltd Figure 9.1a Epinephrine
Ā© 2015 Pearson Education Ltd Concept 9.1: External signals are converted to responses within the cell a) Communication among microorganisms provides some insight into how cells send, receive, and respond to signals
Ā© 2015 Pearson Education Ltd Local and Long-Distance Signaling a) Cells in a multicellular organism communicate via signaling molecules b) In local signaling, animal cells may communicate by direct contact c) Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells d) Signaling substances in the cytosol can pass freely between adjacent cells
Ā© 2015 Pearson Education Ltd Figure 9.4 Plasma membranes Cell wall (a) Cell junctions (b) Cell-cell recognition Gap junctions between animal cells Plasmodesmata between plant cells
Ā© 2015 Pearson Education Ltd a) In many other cases, animal cells communicate using secreted messenger molecules that travel only short distances b) Growth factors, which stimulate nearby target cells to grow and divide, are one class of such local regulators in animals c) This type of local signaling in animals is called paracrine signaling
Ā© 2015 Pearson Education Ltd a) Synaptic signaling occurs in the animal nervous system when a neurotransmitter is released in response to an electric signal b) Local signaling in plants is not well understood beyond communication between plasmodesmata
Ā© 2015 Pearson Education Ltd a) In long-distance signaling, plants and animals use chemicals called hormones b) Hormonal signaling in animals is called endocrine signaling; specialized cells release hormones, which travel to target cells via the circulatory system c) The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal
Ā© 2015 Pearson Education Ltd Figure 9.5 Local signaling Target cells Secreting cell Secretory vesicles Local regulator Target cell (b) Synaptic signaling(a) Paracrine signaling (c) Endocrine (hormonal) signaling Electrical signal triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Long-distance signaling Endocrine cell Target cell specifically binds hormone. Hormone travels in bloodstream. Blood vessel
Ā© 2015 Pearson Education Ltd Figure 9.5a Local signaling Target cells Secreting cell Secretory vesicles Local regulator (a) Paracrine signaling
Ā© 2015 Pearson Education Ltd Figure 9.5b Target cell (b) Synaptic signaling Electrical signal triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Local signaling
Ā© 2015 Pearson Education Ltd Figure 9.5c (c) Endocrine (hormonal) signaling Long-distance signaling Endocrine cell Target cell specifically binds hormone. Hormone travels in bloodstream. Blood vessel
Ā© 2015 Pearson Education Ltd The Three Stages of Cell Signaling: A Preview a) Earl W. Sutherland discovered how the hormone epinephrine acts on cells b) Sutherland suggested that cells receiving signals went through three processes a)Reception b)Transduction c)Response
Ā© 2015 Pearson Education Ltd a) In reception, the target cell detects a signaling molecule that binds to a receptor protein on the cell surface b) In transduction, the binding of the signaling molecule alters the receptor and initiates a signal transduction pathway; transduction often occurs in a series of steps c) In response, the transduced signal triggers a specific response in the target cell
Ā© 2015 Pearson Education Ltd Figure 9.6-1 CYTOPLASM Plasma membrane EXTRACELLULAR FLUID Receptor Signaling molecule Reception1
Ā© 2015 Pearson Education Ltd Figure 9.6-2 CYTOPLASM Plasma membrane EXTRACELLULAR FLUID Receptor Signaling molecule Reception1 Transduction2 Relay molecules 1 2 3
Ā© 2015 Pearson Education Ltd Figure 9.6-3 CYTOPLASM Plasma membrane EXTRACELLULAR FLUID Receptor Signaling molecule Reception1 Transduction2 Relay molecules 1 2 3 Response3 Activation of cellular response
Ā© 2015 Pearson Education Ltd Animation: Overview of Cell Signaling
Ā© 2015 Pearson Education Ltd Concept 9.2: Reception: A signaling molecule binds to a receptor protein, causing it to change shape a) The binding between a signal molecule (ligand) and receptor is highly specific b) A shape change in a receptor is often the initial transduction of the signal c) Most signal receptors are plasma membrane proteins
Ā© 2015 Pearson Education Ltd Receptors in the Plasma Membrane a) G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors b) Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane
Ā© 2015 Pearson Education Ltd Figure 9.7 Plasma membrane Cholesterol Molecule mimicking ligand Ī²2-adrenergic receptors
Ā© 2015 Pearson Education Ltd a) There are three main types of membrane receptors a)G protein-coupled receptors b)Receptor tyrosine kinases c)Ion channel receptors
Ā© 2015 Pearson Education Ltd a) G protein-coupled receptors (GPCRs) are cell surface transmembrane receptors that work with the help of a G protein b) G proteins bind the energy-rich GTP c) G proteins are all very similar in structure d) GPCR systems are extremely widespread and diverse in their functions
Ā© 2015 Pearson Education Ltd a) Receptor tyrosine kinases (RTKs) are membrane receptors that attach phosphates to tyrosines b) A receptor tyrosine kinase can trigger multiple signal transduction pathways at once c) Abnormal functioning of RTKs is associated with many types of cancers
Ā© 2015 Pearson Education Ltd a) A ligand-gated ion channel receptor acts as a gate when the receptor changes shape b) When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2 +, through a channel in the receptor
Ā© 2015 Pearson Education Ltd Figure 9.8a Signaling molecule binding site Segment that interacts with G proteins G protein-coupled receptor
Ā© 2015 Pearson Education Ltd Figure 9.8b Activated enzyme Enzyme G protein (inactive)CYTOPLASM G protein-coupled receptor Plasma membrane Activated receptor Signaling molecule GDP GTP GDP GTP GDP Inactive enzyme Cellular response P i GTP GDP 1 2 43
Ā© 2015 Pearson Education Ltd Figure 9.8ba Enzyme G protein (inactive)CYTOPLASM G protein-coupled receptor Plasma membrane GDP Activated receptor Signaling molecule Inactive enzyme GTP GDP GDP GTP 1 2
Ā© 2015 Pearson Education Ltd Figure 9.8bb Activated enzyme Cellular response 3 GTP GDP P i 4
Ā© 2015 Pearson Education Ltd Figure 9.8c Tyrosines CYTOPLASM Receptor tyrosine kinase proteins (inactive monomers) Tyr Tyr Tyr Tyr Tyr Tyr Ligand-binding site ļ” helix in the membrane Signaling molecule (ligand) Signaling molecule Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Dimer Activated relay proteins Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Inactive relay proteins Cellular response 1 Cellular response 2 P P P P P P P P P P P P Tyr Tyr Tyr Fully activated receptor tyrosine kinase (phos- phorylated dimer) Tyr Tyr Tyr Tyr Tyr Tyr 6 6 ADPATP Activated tyrosine kinase regions (unphosphorylated dimer) 1 2 43
Ā© 2015 Pearson Education Ltd Figure 9.8ca Tyrosines CYTOPLASM Receptor tyrosine kinase proteins (inactive monomers) Ligand-binding site ļ” helix in the membrane Signaling molecule (ligand) Tyr Tyr Tyr Tyr Tyr Tyr 1
Ā© 2015 Pearson Education Ltd Figure 9.8cb Signaling molecule Dimer Tyr Tyr Tyr Tyr Tyr Tyr 2 Tyr Tyr Tyr Tyr Tyr Tyr
Ā© 2015 Pearson Education Ltd Figure 9.8cc 3 Fully activated receptor tyrosine kinase (phos- phorylated dimer) 6 6 ADPATP Activated tyrosine kinase regions (unphosphorylated dimer) Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr P P P P P P
Ā© 2015 Pearson Education Ltd Figure 9.8cd 4 Tyr Tyr Tyr P P P Tyr Tyr Tyr P P P Activated relay proteins Inactive relay proteins Cellular response 1 Cellular response 2
Ā© 2015 Pearson Education Ltd Figure 9.8d-1 1 Ions Plasma membrane Ligand-gated ion channel receptor Gate closedSignaling molecule (ligand)
Ā© 2015 Pearson Education Ltd Figure 9.8d-2 1 Ions Plasma membrane Ligand-gated ion channel receptor Gate closedSignaling molecule (ligand) Gate open2 Cellular response
Ā© 2015 Pearson Education Ltd Figure 9.8d-3 1 Ions Plasma membrane Ligand-gated ion channel receptor Gate closedSignaling molecule (ligand) Gate open2 Cellular response Gate closed3
Ā© 2015 Pearson Education Ltd Intracellular Receptors a) Intracellular receptor proteins are found in the cytoplasm or nucleus of target cells b) Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors c) Examples of hydrophobic messengers are the steroid and thyroid hormones of animals d) An activated hormone-receptor complex can act as a transcription factor, turning on specific genes
Ā© 2015 Pearson Education Ltd Figure 9.9 Hormone (aldosterone) Receptor protein Plasma membrane Hormone- receptor complex EXTRA- CELLULAR FLUID DNA mRNA NUCLEUS New protein CYTOPLASM
Ā© 2015 Pearson Education Ltd Figure 9.9a Hormone (aldosterone) Receptor protein Plasma membrane Hormone- receptor complex EXTRA- CELLULAR FLUID NUCLEUS CYTOPLASM
Ā© 2015 Pearson Education Ltd Figure 9.9b Hormone- receptor complex DNA mRNA NUCLEUS New protein CYTOPLASM
Concept 9.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell a) Signal transduction usually involves multiple steps b) Multistep pathways can greatly amplify a signal c) Multistep pathways provide more opportunities for coordination and regulation of the cellular response Ā© 2015 Pearson Education Ltd
Ā© 2015 Pearson Education Ltd Signal Transduction Pathways a) The binding of a signaling molecule to a receptor triggers the first step in a chain of molecular interactions b) Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated c) At each step, the signal is transduced into a different form, usually a shape change in a protein
Ā© 2015 Pearson Education Ltd Protein Phosphorylation and Dephosphorylation a) Phosphorylation and dephosphorylation of proteins is a widespread cellular mechanism for regulating protein activity b)Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation c) Many relay molecules in signal transduction pathways are protein kinases, creating a phosphorylation cascade
Ā© 2015 Pearson Education Ltd Figure 9.10 Signaling molecule Activated relay molecule Receptor Inactive protein kinase 1 Inactive protein kinase 2 Inactive protein kinase 3 Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 Active protein Inactive protein ATP ADP PP ATP ADP P i P P P i ATP ADP PP PP P i P Cellular response
Ā© 2015 Pearson Education Ltd Figure 9.10a Signaling molecule Activated relay molecule Receptor Inactive protein kinase 1 Active protein kinase 1
Ā© 2015 Pearson Education Ltd Figure 9.10b Inactive protein kinase 1 Inactive protein kinase 2 Inactive protein kinase 3 Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 ATP ADP PP P i ATP ADP PP P i Phosphorylation cascade P P
Ā© 2015 Pearson Education Ltd Figure 9.10c Inactive protein kinase 3 Active protein kinase 3 ATP ADP PP P i P i P P ATP ADP PP Inactive protein Active protein Cellular response
Ā© 2015 Pearson Education Ltd a) Protein phosphatases rapidly remove the phosphates from proteins, a process called dephosphorylation b) This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off or up or down, as required
Ā© 2015 Pearson Education Ltd Small Molecules and Ions as Second Messengers a) Many signaling pathways involve second messengers b)Second messengers are small, nonprotein, water- soluble molecules or ions that spread throughout a cell by diffusion c) Second messengers participate in pathways initiated by GPCRs and RTKs d) Cyclic AMP and calcium ions are common second messengers
Ā© 2015 Pearson Education Ltd Cyclic AMP a) Cyclic AMP (cAMP) is one of the most widely used second messengers b)Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal
Ā© 2015 Pearson Education Ltd Figure 9.11 ATP cAMP AMP PhosphodiesteraseAdenylyl cyclase Pyrophosphate H2O
Ā© 2015 Pearson Education Ltd Figure 9.11a ATP cAMP Adenylyl cyclase Pyrophosphate
Ā© 2015 Pearson Education Ltd Figure 9.11b cAMP AMP H2O Phosphodiesterase
Ā© 2015 Pearson Education Ltd a) Many signal molecules trigger formation of cAMP b) Other components of cAMP pathways are G proteins, G protein-coupled receptors, and protein kinases c) cAMP usually activates protein kinase A, which phosphorylates various other proteins d) Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase
Ā© 2015 Pearson Education Ltd Figure 9.12 First messenger (signaling molecule such as epinephrine) G protein Adenylyl cyclase G protein-coupled receptor Second messenger Cellular responses Protein kinase A GTP ATP cAMP
Ā© 2015 Pearson Education Ltd a) Understanding of the role of cAMP in G protein signaling pathways helps explain how certain microbes cause disease b) The cholera bacterium, Vibrio cholerae, produces a toxin that modifies a G protein so that it is stuck in its active form c) This modified G protein continually makes cAMP, causing intestinal cells to secrete large amounts of salt into the intestines d) Water follows by osmosis and an untreated person can soon die from loss of water and salt
Ā© 2015 Pearson Education Ltd Calcium Ions and Inositol Triphosphate (IP3) a) Calcium ions (Ca2 +) act as a second messenger in many pathways b) Ca2 + can function as a second messenger because its concentration in the cytosol is normally much lower than the concentration outside the cell c) A small change in number of calcium ions thus represents a relatively large percentage change in calcium concentration
Ā© 2015 Pearson Education Ltd Figure 9.13 Endoplasmic reticulum (ER) Plasma membrane Mitochondrion ATP ATP ATPCYTOSOL Nucleus Ca2+ pump EXTRACELLULAR FLUID Key High [Ca2+] Low [Ca2+]
Ā© 2015 Pearson Education Ltd a) A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol b) Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers c) These two are produced by cleavage of a certain phospholipid in the plasma membrane
Ā© 2015 Pearson Education Ltd Figure 9.14-1 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein GTP CYTOSOL G protein-coupled receptor Phospholipase C DAG PIP2 IP3 (second messenger) IP3-gated calcium channel Ca2+ Nucleus Endoplasmic reticulum (ER) lumen
Ā© 2015 Pearson Education Ltd Figure 9.14-2 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein GTP CYTOSOL G protein-coupled receptor Phospholipase C DAG PIP2 IP3 (second messenger) IP3-gated calcium channel Ca2+ Nucleus Endoplasmic reticulum (ER) lumen Ca2+ (second messenger)
Ā© 2015 Pearson Education Ltd Figure 9.14-3 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein GTP CYTOSOL G protein-coupled receptor Phospholipase C DAG PIP2 IP3 (second messenger) IP3-gated calcium channel Ca2+ Nucleus Endoplasmic reticulum (ER) lumen Ca2+ (second messenger) Various proteins activated Cellular responses
Ā© 2015 Pearson Education Ltd Animation: Signal Transduction Pathways
Concept 9.4: Response: Cell signaling leads to regulation of transcription or cytoplasmic activities a) The cellā€™s response to an extracellular signal is called the ā€œoutput responseā€ Ā© 2015 Pearson Education Ltd
Ā© 2015 Pearson Education Ltd Nuclear and Cytoplasmic Responses a) Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities b) The response may occur in the cytoplasm or in the nucleus c) Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus d) The final activated molecule in the signaling pathway may function as a transcription factor
Ā© 2015 Pearson Education Ltd Figure 9.15 Growth factor Receptor Phospho- rylation cascade Reception Transduction CYTOPLASM Inactive transcription factor Active transcription factor DNA Response P Gene mRNANUCLEUS
Ā© 2015 Pearson Education Ltd Figure 9.15a Growth factor Receptor Phospho- rylation cascade Reception Transduction NUCLEUS CYTOPLASM Inactive transcription factor
Ā© 2015 Pearson Education Ltd Figure 9.15b NUCLEUS CYTOPLASM Phospho- rylation cascade Transduction Inactive transcription factor Active transcription factor Response DNA P Gene mRNA
Ā© 2015 Pearson Education Ltd a) Other pathways regulate the activity of enzymes rather than their synthesis b) For example, a signal could cause opening or closing of an ion channel in the plasma membrane, or a change in cell metabolism
Ā© 2015 Pearson Education Ltd Figure 9.16 Reception Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Inactive phosphorylase kinase Active phosphorylase kinase (105) Active glycogen phosphorylase (106) Inactive glycogen phosphorylase Glycogen Response Glucose 1-phosphate (108 molecules) Binding of epinephrine to G protein-coupled receptor (1 molecule)
Ā© 2015 Pearson Education Ltd Figure 9.16a Reception Glycogen Response Glucose 1-phosphate (108 molecules) Binding of epinephrine to G protein-coupled receptor (1 molecule)
Ā© 2015 Pearson Education Ltd Figure 9.16b Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104)
Ā© 2015 Pearson Education Ltd Figure 9.16c Inactive phosphorylase kinase Active phosphorylase kinase (105) Active glycogen phosphorylase (106) Inactive glycogen phosphorylase Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Transduction
Ā© 2015 Pearson Education Ltd a) Signaling pathways can also affect the overall behavior of a cell, for example, a signal could lead to cell division
Ā© 2015 Pearson Education Ltd Regulation of the Response a) A response to a signal may not be simply ā€œonā€ or ā€œoffā€ b) There are four aspects of signal regulation to consider a)Amplification of the signal (and thus the response) b)Specificity of the response c)Overall efficiency of response, enhanced by scaffolding proteins d)Termination of the signal
Ā© 2015 Pearson Education Ltd Signal Amplification a) Enzyme cascades amplify the cellā€™s response to the signal b) At each step, the number of activated products is much greater than in the preceding step
Ā© 2015 Pearson Education Ltd The Specificity of Cell Signaling and Coordination of the Response a) Different kinds of cells have different collections of proteins b) These different proteins allow cells to detect and respond to different signals c) The same signal can have different effects in cells with different proteins and pathways d) Pathway branching and ā€œcross-talkā€ further help the cell coordinate incoming signals
Ā© 2015 Pearson Education Ltd Figure 9.17 Signaling molecule Receptor Relay mole- cules Response 1 Response 2 Response 3 Response 4 Response 5 Cell A: Pathway leads to a single response. Cell B: Pathway branches, leading to two responses. Cell C: Cross-talk occurs between two pathways. Cell D: Different receptor leads to a different response. Activation or inhibition
Ā© 2015 Pearson Education Ltd Figure 9.17a Signaling molecule Receptor Relay mole- cules Response 1 Response 2 Response 3 Cell A: Pathway leads to a single response. Cell B: Pathway branches, leading to two responses.
Ā© 2015 Pearson Education Ltd Figure 9.17b Response 4 Response 5 Cell C: Cross-talk occurs between two pathways. Cell D: Different receptor leads to a different response. Activation or inhibition
Ā© 2015 Pearson Education Ltd Signaling Efficiency: Scaffolding Proteins and Signaling Complexes a) Scaffolding proteins are large relay proteins to which other relay proteins are attached b) Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway c) In some cases, scaffolding proteins may also help activate some of the relay proteins
Ā© 2015 Pearson Education Ltd Figure 9.18 Signaling molecule Receptor Scaffolding protein Plasma membrane Three different protein kinases
Ā© 2015 Pearson Education Ltd Termination of the Signal a) Inactivation mechanisms are an essential aspect of cell signaling b) If ligand concentration falls, fewer receptors will be bound c) Unbound receptors revert to an inactive state
Ā© 2015 Pearson Education Ltd Concept 9.5: Apoptosis integrates multiple cell-signaling pathways a) Cells that are infected or damaged or have reached the end of their functional lives often undergo ā€œprogrammed cell deathā€ b)Apoptosis is the best understood type c) Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells d) Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells
Ā© 2015 Pearson Education Ltd Figure 9.19 2 Āµm
Ā© 2015 Pearson Education Ltd Apoptosis in the Soil Worm Caenorhabditis elegans a) In worms and other organisms, apoptosis is triggered by signals that activate a cascade of ā€œsuicideā€ proteins in the cells programmed to die b) When the death signal is received, an apoptosis inhibiting protein (Ced-9) is inactivated, triggering a cascade of caspase proteins that promote apoptosis c) The chief caspase in the nematode is called Ced-3
Ā© 2015 Pearson Education Ltd Figure 9.20 Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Receptor for death- signaling molecule (a) No death signal (b) Death signal Ced-4 Ced-3 Inactive proteins Death- signaling molecule Ced-9 (inactive) Active Ced-4 Active Ced-3 Cell forms blebs Other proteases Nucleases Activation cascade
Ā© 2015 Pearson Education Ltd Figure 9.20a Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Receptor for death- signaling molecule (a) No death signal Ced-4 Ced-3 Inactive proteins
Ā© 2015 Pearson Education Ltd Figure 9.20b (b) Death signal Death- signaling molecule Ced-9 (inactive) Active Ced-4 Active Ced-3 Cell forms blebs Other proteases Nucleases Activation cascade
Ā© 2015 Pearson Education Ltd Apoptotic Pathways and the Signals That Trigger Them a) In humans and other mammals, several different pathways, including about 15 caspases, can carry out apoptosis b) Apoptosis can be triggered by signals from outside the cell or inside it c) Internal signals can result from irreparable DNA damage or excessive protein misfolding
Ā© 2015 Pearson Education Ltd a) Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals b) For example, apoptosis is a normal part of development of hands and feet in humans (and paws in other mammals) c) Apoptosis may be involved in some diseases (for example, Parkinsonā€™s and Alzheimerā€™s); interference with apoptosis may contribute to some cancers
Ā© 2015 Pearson Education Ltd Figure 9.21 Interdigital tissue 1 mm Cells undergoing apoptosis Space between digits
Ā© 2015 Pearson Education Ltd Figure 9.21a Interdigital tissue1 mm
Ā© 2015 Pearson Education Ltd Figure 9.21b 1 mm Cells undergoing apoptosis
Ā© 2015 Pearson Education Ltd Figure 9.21c Space between digits1 mm
Ā© 2015 Pearson Education Ltd Figure 9.UN01a Mating factor Mating factor activates receptor. GDP G protein binds GTP and becomes activated. GTP Fus3 Fus3 P Phosphoryl- ation cascade Phosphorylation cascade activates Fus3, which moves to plasma membrane. Formin Formin P Fus3 phos- phorylates formin, activating it. Formin initiates growth of microfilaments that form the shmoo projections. Microfilament P P Fus3 Actin subunit Formin Shmoo projection formingG protein-coupled receptor 1 2 5 4 3
Ā© 2015 Pearson Education Ltd Figure 9.UN01aa Mating factor Mating factor activates receptor. GDP G protein binds GTP and becomes activated. GTP Fus3 Fus3 P Phosphoryl- ation cascade Phosphorylation cascade activates Fus3, which moves to plasma membrane. G protein-coupled receptor 1 2 3
Ā© 2015 Pearson Education Ltd Figure 9.UN01ab Formin Formin P Fus3 phos- phorylates formin, activating it. Formin initiates growth of microfilaments that form the shmoo projections. Microfilament P P Fus3 Actin subunit Formin Shmoo projection forming 4 5
Ā© 2015 Pearson Education Ltd Figure 9.UN01b Wild type
Ā© 2015 Pearson Education Ltd Figure 9.UN01c ļ„Fus3
Ā© 2015 Pearson Education Ltd Figure 9.UN01d ļ„formin
Ā© 2015 Pearson Education Ltd Figure 9.UN02 Reception Transduction Response Relay molecules Signaling molecule Receptor Activation of cellular response 1 2 3 1 2 3
Ā© 2015 Pearson Education Ltd Figure 9.UN03

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09 ge lecture presentation

  • 1. BIOLOGY Campbell ā€¢ Reece ā€¢ Urry ā€¢ Cain ā€¢ Wasserman ā€¢ Minorsky ā€¢ Jackson Ā© 2015 Pearson Education Ltd TENTH EDITION Global Edition Lecture Presentation by Nicole Tunbridge and Kathleen Fitzpatrick 9 Cellular Signaling
  • 2. Ā© 2015 Pearson Education Ltd Cellular Messaging a) Cells can signal to each other and interpret the signals they receive from other cells and the environment b) Signals are most often chemicals c) The same small set of cell signaling mechanisms shows up in diverse species and processes
  • 3. Ā© 2015 Pearson Education Ltd Figure 9.1a Epinephrine
  • 4. Ā© 2015 Pearson Education Ltd Concept 9.1: External signals are converted to responses within the cell a) Communication among microorganisms provides some insight into how cells send, receive, and respond to signals
  • 5. Ā© 2015 Pearson Education Ltd Local and Long-Distance Signaling a) Cells in a multicellular organism communicate via signaling molecules b) In local signaling, animal cells may communicate by direct contact c) Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells d) Signaling substances in the cytosol can pass freely between adjacent cells
  • 6. Ā© 2015 Pearson Education Ltd Figure 9.4 Plasma membranes Cell wall (a) Cell junctions (b) Cell-cell recognition Gap junctions between animal cells Plasmodesmata between plant cells
  • 7. Ā© 2015 Pearson Education Ltd a) In many other cases, animal cells communicate using secreted messenger molecules that travel only short distances b) Growth factors, which stimulate nearby target cells to grow and divide, are one class of such local regulators in animals c) This type of local signaling in animals is called paracrine signaling
  • 8. Ā© 2015 Pearson Education Ltd a) Synaptic signaling occurs in the animal nervous system when a neurotransmitter is released in response to an electric signal b) Local signaling in plants is not well understood beyond communication between plasmodesmata
  • 9. Ā© 2015 Pearson Education Ltd a) In long-distance signaling, plants and animals use chemicals called hormones b) Hormonal signaling in animals is called endocrine signaling; specialized cells release hormones, which travel to target cells via the circulatory system c) The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal
  • 10. Ā© 2015 Pearson Education Ltd Figure 9.5 Local signaling Target cells Secreting cell Secretory vesicles Local regulator Target cell (b) Synaptic signaling(a) Paracrine signaling (c) Endocrine (hormonal) signaling Electrical signal triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Long-distance signaling Endocrine cell Target cell specifically binds hormone. Hormone travels in bloodstream. Blood vessel
  • 11. Ā© 2015 Pearson Education Ltd Figure 9.5a Local signaling Target cells Secreting cell Secretory vesicles Local regulator (a) Paracrine signaling
  • 12. Ā© 2015 Pearson Education Ltd Figure 9.5b Target cell (b) Synaptic signaling Electrical signal triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Local signaling
  • 13. Ā© 2015 Pearson Education Ltd Figure 9.5c (c) Endocrine (hormonal) signaling Long-distance signaling Endocrine cell Target cell specifically binds hormone. Hormone travels in bloodstream. Blood vessel
  • 14. Ā© 2015 Pearson Education Ltd The Three Stages of Cell Signaling: A Preview a) Earl W. Sutherland discovered how the hormone epinephrine acts on cells b) Sutherland suggested that cells receiving signals went through three processes a)Reception b)Transduction c)Response
  • 15. Ā© 2015 Pearson Education Ltd a) In reception, the target cell detects a signaling molecule that binds to a receptor protein on the cell surface b) In transduction, the binding of the signaling molecule alters the receptor and initiates a signal transduction pathway; transduction often occurs in a series of steps c) In response, the transduced signal triggers a specific response in the target cell
  • 16. Ā© 2015 Pearson Education Ltd Figure 9.6-1 CYTOPLASM Plasma membrane EXTRACELLULAR FLUID Receptor Signaling molecule Reception1
  • 17. Ā© 2015 Pearson Education Ltd Figure 9.6-2 CYTOPLASM Plasma membrane EXTRACELLULAR FLUID Receptor Signaling molecule Reception1 Transduction2 Relay molecules 1 2 3
  • 18. Ā© 2015 Pearson Education Ltd Figure 9.6-3 CYTOPLASM Plasma membrane EXTRACELLULAR FLUID Receptor Signaling molecule Reception1 Transduction2 Relay molecules 1 2 3 Response3 Activation of cellular response
  • 19. Ā© 2015 Pearson Education Ltd Animation: Overview of Cell Signaling
  • 20. Ā© 2015 Pearson Education Ltd Concept 9.2: Reception: A signaling molecule binds to a receptor protein, causing it to change shape a) The binding between a signal molecule (ligand) and receptor is highly specific b) A shape change in a receptor is often the initial transduction of the signal c) Most signal receptors are plasma membrane proteins
  • 21. Ā© 2015 Pearson Education Ltd Receptors in the Plasma Membrane a) G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors b) Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane
  • 22. Ā© 2015 Pearson Education Ltd Figure 9.7 Plasma membrane Cholesterol Molecule mimicking ligand Ī²2-adrenergic receptors
  • 23. Ā© 2015 Pearson Education Ltd a) There are three main types of membrane receptors a)G protein-coupled receptors b)Receptor tyrosine kinases c)Ion channel receptors
  • 24. Ā© 2015 Pearson Education Ltd a) G protein-coupled receptors (GPCRs) are cell surface transmembrane receptors that work with the help of a G protein b) G proteins bind the energy-rich GTP c) G proteins are all very similar in structure d) GPCR systems are extremely widespread and diverse in their functions
  • 25. Ā© 2015 Pearson Education Ltd a) Receptor tyrosine kinases (RTKs) are membrane receptors that attach phosphates to tyrosines b) A receptor tyrosine kinase can trigger multiple signal transduction pathways at once c) Abnormal functioning of RTKs is associated with many types of cancers
  • 26. Ā© 2015 Pearson Education Ltd a) A ligand-gated ion channel receptor acts as a gate when the receptor changes shape b) When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2 +, through a channel in the receptor
  • 27. Ā© 2015 Pearson Education Ltd Figure 9.8a Signaling molecule binding site Segment that interacts with G proteins G protein-coupled receptor
  • 28. Ā© 2015 Pearson Education Ltd Figure 9.8b Activated enzyme Enzyme G protein (inactive)CYTOPLASM G protein-coupled receptor Plasma membrane Activated receptor Signaling molecule GDP GTP GDP GTP GDP Inactive enzyme Cellular response P i GTP GDP 1 2 43
  • 29. Ā© 2015 Pearson Education Ltd Figure 9.8ba Enzyme G protein (inactive)CYTOPLASM G protein-coupled receptor Plasma membrane GDP Activated receptor Signaling molecule Inactive enzyme GTP GDP GDP GTP 1 2
  • 30. Ā© 2015 Pearson Education Ltd Figure 9.8bb Activated enzyme Cellular response 3 GTP GDP P i 4
  • 31. Ā© 2015 Pearson Education Ltd Figure 9.8c Tyrosines CYTOPLASM Receptor tyrosine kinase proteins (inactive monomers) Tyr Tyr Tyr Tyr Tyr Tyr Ligand-binding site ļ” helix in the membrane Signaling molecule (ligand) Signaling molecule Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Dimer Activated relay proteins Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Inactive relay proteins Cellular response 1 Cellular response 2 P P P P P P P P P P P P Tyr Tyr Tyr Fully activated receptor tyrosine kinase (phos- phorylated dimer) Tyr Tyr Tyr Tyr Tyr Tyr 6 6 ADPATP Activated tyrosine kinase regions (unphosphorylated dimer) 1 2 43
  • 32. Ā© 2015 Pearson Education Ltd Figure 9.8ca Tyrosines CYTOPLASM Receptor tyrosine kinase proteins (inactive monomers) Ligand-binding site ļ” helix in the membrane Signaling molecule (ligand) Tyr Tyr Tyr Tyr Tyr Tyr 1
  • 33. Ā© 2015 Pearson Education Ltd Figure 9.8cb Signaling molecule Dimer Tyr Tyr Tyr Tyr Tyr Tyr 2 Tyr Tyr Tyr Tyr Tyr Tyr
  • 34. Ā© 2015 Pearson Education Ltd Figure 9.8cc 3 Fully activated receptor tyrosine kinase (phos- phorylated dimer) 6 6 ADPATP Activated tyrosine kinase regions (unphosphorylated dimer) Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr P P P P P P
  • 35. Ā© 2015 Pearson Education Ltd Figure 9.8cd 4 Tyr Tyr Tyr P P P Tyr Tyr Tyr P P P Activated relay proteins Inactive relay proteins Cellular response 1 Cellular response 2
  • 36. Ā© 2015 Pearson Education Ltd Figure 9.8d-1 1 Ions Plasma membrane Ligand-gated ion channel receptor Gate closedSignaling molecule (ligand)
  • 37. Ā© 2015 Pearson Education Ltd Figure 9.8d-2 1 Ions Plasma membrane Ligand-gated ion channel receptor Gate closedSignaling molecule (ligand) Gate open2 Cellular response
  • 38. Ā© 2015 Pearson Education Ltd Figure 9.8d-3 1 Ions Plasma membrane Ligand-gated ion channel receptor Gate closedSignaling molecule (ligand) Gate open2 Cellular response Gate closed3
  • 39. Ā© 2015 Pearson Education Ltd Intracellular Receptors a) Intracellular receptor proteins are found in the cytoplasm or nucleus of target cells b) Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors c) Examples of hydrophobic messengers are the steroid and thyroid hormones of animals d) An activated hormone-receptor complex can act as a transcription factor, turning on specific genes
  • 40. Ā© 2015 Pearson Education Ltd Figure 9.9 Hormone (aldosterone) Receptor protein Plasma membrane Hormone- receptor complex EXTRA- CELLULAR FLUID DNA mRNA NUCLEUS New protein CYTOPLASM
  • 41. Ā© 2015 Pearson Education Ltd Figure 9.9a Hormone (aldosterone) Receptor protein Plasma membrane Hormone- receptor complex EXTRA- CELLULAR FLUID NUCLEUS CYTOPLASM
  • 42. Ā© 2015 Pearson Education Ltd Figure 9.9b Hormone- receptor complex DNA mRNA NUCLEUS New protein CYTOPLASM
  • 43. Concept 9.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell a) Signal transduction usually involves multiple steps b) Multistep pathways can greatly amplify a signal c) Multistep pathways provide more opportunities for coordination and regulation of the cellular response Ā© 2015 Pearson Education Ltd
  • 44. Ā© 2015 Pearson Education Ltd Signal Transduction Pathways a) The binding of a signaling molecule to a receptor triggers the first step in a chain of molecular interactions b) Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated c) At each step, the signal is transduced into a different form, usually a shape change in a protein
  • 45. Ā© 2015 Pearson Education Ltd Protein Phosphorylation and Dephosphorylation a) Phosphorylation and dephosphorylation of proteins is a widespread cellular mechanism for regulating protein activity b)Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation c) Many relay molecules in signal transduction pathways are protein kinases, creating a phosphorylation cascade
  • 46. Ā© 2015 Pearson Education Ltd Figure 9.10 Signaling molecule Activated relay molecule Receptor Inactive protein kinase 1 Inactive protein kinase 2 Inactive protein kinase 3 Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 Active protein Inactive protein ATP ADP PP ATP ADP P i P P P i ATP ADP PP PP P i P Cellular response
  • 47. Ā© 2015 Pearson Education Ltd Figure 9.10a Signaling molecule Activated relay molecule Receptor Inactive protein kinase 1 Active protein kinase 1
  • 48. Ā© 2015 Pearson Education Ltd Figure 9.10b Inactive protein kinase 1 Inactive protein kinase 2 Inactive protein kinase 3 Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 ATP ADP PP P i ATP ADP PP P i Phosphorylation cascade P P
  • 49. Ā© 2015 Pearson Education Ltd Figure 9.10c Inactive protein kinase 3 Active protein kinase 3 ATP ADP PP P i P i P P ATP ADP PP Inactive protein Active protein Cellular response
  • 50. Ā© 2015 Pearson Education Ltd a) Protein phosphatases rapidly remove the phosphates from proteins, a process called dephosphorylation b) This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off or up or down, as required
  • 51. Ā© 2015 Pearson Education Ltd Small Molecules and Ions as Second Messengers a) Many signaling pathways involve second messengers b)Second messengers are small, nonprotein, water- soluble molecules or ions that spread throughout a cell by diffusion c) Second messengers participate in pathways initiated by GPCRs and RTKs d) Cyclic AMP and calcium ions are common second messengers
  • 52. Ā© 2015 Pearson Education Ltd Cyclic AMP a) Cyclic AMP (cAMP) is one of the most widely used second messengers b)Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal
  • 53. Ā© 2015 Pearson Education Ltd Figure 9.11 ATP cAMP AMP PhosphodiesteraseAdenylyl cyclase Pyrophosphate H2O
  • 54. Ā© 2015 Pearson Education Ltd Figure 9.11a ATP cAMP Adenylyl cyclase Pyrophosphate
  • 55. Ā© 2015 Pearson Education Ltd Figure 9.11b cAMP AMP H2O Phosphodiesterase
  • 56. Ā© 2015 Pearson Education Ltd a) Many signal molecules trigger formation of cAMP b) Other components of cAMP pathways are G proteins, G protein-coupled receptors, and protein kinases c) cAMP usually activates protein kinase A, which phosphorylates various other proteins d) Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase
  • 57. Ā© 2015 Pearson Education Ltd Figure 9.12 First messenger (signaling molecule such as epinephrine) G protein Adenylyl cyclase G protein-coupled receptor Second messenger Cellular responses Protein kinase A GTP ATP cAMP
  • 58. Ā© 2015 Pearson Education Ltd a) Understanding of the role of cAMP in G protein signaling pathways helps explain how certain microbes cause disease b) The cholera bacterium, Vibrio cholerae, produces a toxin that modifies a G protein so that it is stuck in its active form c) This modified G protein continually makes cAMP, causing intestinal cells to secrete large amounts of salt into the intestines d) Water follows by osmosis and an untreated person can soon die from loss of water and salt
  • 59. Ā© 2015 Pearson Education Ltd Calcium Ions and Inositol Triphosphate (IP3) a) Calcium ions (Ca2 +) act as a second messenger in many pathways b) Ca2 + can function as a second messenger because its concentration in the cytosol is normally much lower than the concentration outside the cell c) A small change in number of calcium ions thus represents a relatively large percentage change in calcium concentration
  • 60. Ā© 2015 Pearson Education Ltd Figure 9.13 Endoplasmic reticulum (ER) Plasma membrane Mitochondrion ATP ATP ATPCYTOSOL Nucleus Ca2+ pump EXTRACELLULAR FLUID Key High [Ca2+] Low [Ca2+]
  • 61. Ā© 2015 Pearson Education Ltd a) A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol b) Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers c) These two are produced by cleavage of a certain phospholipid in the plasma membrane
  • 62. Ā© 2015 Pearson Education Ltd Figure 9.14-1 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein GTP CYTOSOL G protein-coupled receptor Phospholipase C DAG PIP2 IP3 (second messenger) IP3-gated calcium channel Ca2+ Nucleus Endoplasmic reticulum (ER) lumen
  • 63. Ā© 2015 Pearson Education Ltd Figure 9.14-2 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein GTP CYTOSOL G protein-coupled receptor Phospholipase C DAG PIP2 IP3 (second messenger) IP3-gated calcium channel Ca2+ Nucleus Endoplasmic reticulum (ER) lumen Ca2+ (second messenger)
  • 64. Ā© 2015 Pearson Education Ltd Figure 9.14-3 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein GTP CYTOSOL G protein-coupled receptor Phospholipase C DAG PIP2 IP3 (second messenger) IP3-gated calcium channel Ca2+ Nucleus Endoplasmic reticulum (ER) lumen Ca2+ (second messenger) Various proteins activated Cellular responses
  • 65. Ā© 2015 Pearson Education Ltd Animation: Signal Transduction Pathways
  • 66. Concept 9.4: Response: Cell signaling leads to regulation of transcription or cytoplasmic activities a) The cellā€™s response to an extracellular signal is called the ā€œoutput responseā€ Ā© 2015 Pearson Education Ltd
  • 67. Ā© 2015 Pearson Education Ltd Nuclear and Cytoplasmic Responses a) Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities b) The response may occur in the cytoplasm or in the nucleus c) Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus d) The final activated molecule in the signaling pathway may function as a transcription factor
  • 68. Ā© 2015 Pearson Education Ltd Figure 9.15 Growth factor Receptor Phospho- rylation cascade Reception Transduction CYTOPLASM Inactive transcription factor Active transcription factor DNA Response P Gene mRNANUCLEUS
  • 69. Ā© 2015 Pearson Education Ltd Figure 9.15a Growth factor Receptor Phospho- rylation cascade Reception Transduction NUCLEUS CYTOPLASM Inactive transcription factor
  • 70. Ā© 2015 Pearson Education Ltd Figure 9.15b NUCLEUS CYTOPLASM Phospho- rylation cascade Transduction Inactive transcription factor Active transcription factor Response DNA P Gene mRNA
  • 71. Ā© 2015 Pearson Education Ltd a) Other pathways regulate the activity of enzymes rather than their synthesis b) For example, a signal could cause opening or closing of an ion channel in the plasma membrane, or a change in cell metabolism
  • 72. Ā© 2015 Pearson Education Ltd Figure 9.16 Reception Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Inactive phosphorylase kinase Active phosphorylase kinase (105) Active glycogen phosphorylase (106) Inactive glycogen phosphorylase Glycogen Response Glucose 1-phosphate (108 molecules) Binding of epinephrine to G protein-coupled receptor (1 molecule)
  • 73. Ā© 2015 Pearson Education Ltd Figure 9.16a Reception Glycogen Response Glucose 1-phosphate (108 molecules) Binding of epinephrine to G protein-coupled receptor (1 molecule)
  • 74. Ā© 2015 Pearson Education Ltd Figure 9.16b Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104)
  • 75. Ā© 2015 Pearson Education Ltd Figure 9.16c Inactive phosphorylase kinase Active phosphorylase kinase (105) Active glycogen phosphorylase (106) Inactive glycogen phosphorylase Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Transduction
  • 76. Ā© 2015 Pearson Education Ltd a) Signaling pathways can also affect the overall behavior of a cell, for example, a signal could lead to cell division
  • 77. Ā© 2015 Pearson Education Ltd Regulation of the Response a) A response to a signal may not be simply ā€œonā€ or ā€œoffā€ b) There are four aspects of signal regulation to consider a)Amplification of the signal (and thus the response) b)Specificity of the response c)Overall efficiency of response, enhanced by scaffolding proteins d)Termination of the signal
  • 78. Ā© 2015 Pearson Education Ltd Signal Amplification a) Enzyme cascades amplify the cellā€™s response to the signal b) At each step, the number of activated products is much greater than in the preceding step
  • 79. Ā© 2015 Pearson Education Ltd The Specificity of Cell Signaling and Coordination of the Response a) Different kinds of cells have different collections of proteins b) These different proteins allow cells to detect and respond to different signals c) The same signal can have different effects in cells with different proteins and pathways d) Pathway branching and ā€œcross-talkā€ further help the cell coordinate incoming signals
  • 80. Ā© 2015 Pearson Education Ltd Figure 9.17 Signaling molecule Receptor Relay mole- cules Response 1 Response 2 Response 3 Response 4 Response 5 Cell A: Pathway leads to a single response. Cell B: Pathway branches, leading to two responses. Cell C: Cross-talk occurs between two pathways. Cell D: Different receptor leads to a different response. Activation or inhibition
  • 81. Ā© 2015 Pearson Education Ltd Figure 9.17a Signaling molecule Receptor Relay mole- cules Response 1 Response 2 Response 3 Cell A: Pathway leads to a single response. Cell B: Pathway branches, leading to two responses.
  • 82. Ā© 2015 Pearson Education Ltd Figure 9.17b Response 4 Response 5 Cell C: Cross-talk occurs between two pathways. Cell D: Different receptor leads to a different response. Activation or inhibition
  • 83. Ā© 2015 Pearson Education Ltd Signaling Efficiency: Scaffolding Proteins and Signaling Complexes a) Scaffolding proteins are large relay proteins to which other relay proteins are attached b) Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway c) In some cases, scaffolding proteins may also help activate some of the relay proteins
  • 84. Ā© 2015 Pearson Education Ltd Figure 9.18 Signaling molecule Receptor Scaffolding protein Plasma membrane Three different protein kinases
  • 85. Ā© 2015 Pearson Education Ltd Termination of the Signal a) Inactivation mechanisms are an essential aspect of cell signaling b) If ligand concentration falls, fewer receptors will be bound c) Unbound receptors revert to an inactive state
  • 86. Ā© 2015 Pearson Education Ltd Concept 9.5: Apoptosis integrates multiple cell-signaling pathways a) Cells that are infected or damaged or have reached the end of their functional lives often undergo ā€œprogrammed cell deathā€ b)Apoptosis is the best understood type c) Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells d) Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells
  • 87. Ā© 2015 Pearson Education Ltd Figure 9.19 2 Āµm
  • 88. Ā© 2015 Pearson Education Ltd Apoptosis in the Soil Worm Caenorhabditis elegans a) In worms and other organisms, apoptosis is triggered by signals that activate a cascade of ā€œsuicideā€ proteins in the cells programmed to die b) When the death signal is received, an apoptosis inhibiting protein (Ced-9) is inactivated, triggering a cascade of caspase proteins that promote apoptosis c) The chief caspase in the nematode is called Ced-3
  • 89. Ā© 2015 Pearson Education Ltd Figure 9.20 Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Receptor for death- signaling molecule (a) No death signal (b) Death signal Ced-4 Ced-3 Inactive proteins Death- signaling molecule Ced-9 (inactive) Active Ced-4 Active Ced-3 Cell forms blebs Other proteases Nucleases Activation cascade
  • 90. Ā© 2015 Pearson Education Ltd Figure 9.20a Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Receptor for death- signaling molecule (a) No death signal Ced-4 Ced-3 Inactive proteins
  • 91. Ā© 2015 Pearson Education Ltd Figure 9.20b (b) Death signal Death- signaling molecule Ced-9 (inactive) Active Ced-4 Active Ced-3 Cell forms blebs Other proteases Nucleases Activation cascade
  • 92. Ā© 2015 Pearson Education Ltd Apoptotic Pathways and the Signals That Trigger Them a) In humans and other mammals, several different pathways, including about 15 caspases, can carry out apoptosis b) Apoptosis can be triggered by signals from outside the cell or inside it c) Internal signals can result from irreparable DNA damage or excessive protein misfolding
  • 93. Ā© 2015 Pearson Education Ltd a) Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals b) For example, apoptosis is a normal part of development of hands and feet in humans (and paws in other mammals) c) Apoptosis may be involved in some diseases (for example, Parkinsonā€™s and Alzheimerā€™s); interference with apoptosis may contribute to some cancers
  • 94. Ā© 2015 Pearson Education Ltd Figure 9.21 Interdigital tissue 1 mm Cells undergoing apoptosis Space between digits
  • 95. Ā© 2015 Pearson Education Ltd Figure 9.21a Interdigital tissue1 mm
  • 96. Ā© 2015 Pearson Education Ltd Figure 9.21b 1 mm Cells undergoing apoptosis
  • 97. Ā© 2015 Pearson Education Ltd Figure 9.21c Space between digits1 mm
  • 98. Ā© 2015 Pearson Education Ltd Figure 9.UN01a Mating factor Mating factor activates receptor. GDP G protein binds GTP and becomes activated. GTP Fus3 Fus3 P Phosphoryl- ation cascade Phosphorylation cascade activates Fus3, which moves to plasma membrane. Formin Formin P Fus3 phos- phorylates formin, activating it. Formin initiates growth of microfilaments that form the shmoo projections. Microfilament P P Fus3 Actin subunit Formin Shmoo projection formingG protein-coupled receptor 1 2 5 4 3
  • 99. Ā© 2015 Pearson Education Ltd Figure 9.UN01aa Mating factor Mating factor activates receptor. GDP G protein binds GTP and becomes activated. GTP Fus3 Fus3 P Phosphoryl- ation cascade Phosphorylation cascade activates Fus3, which moves to plasma membrane. G protein-coupled receptor 1 2 3
  • 100. Ā© 2015 Pearson Education Ltd Figure 9.UN01ab Formin Formin P Fus3 phos- phorylates formin, activating it. Formin initiates growth of microfilaments that form the shmoo projections. Microfilament P P Fus3 Actin subunit Formin Shmoo projection forming 4 5
  • 101. Ā© 2015 Pearson Education Ltd Figure 9.UN01b Wild type
  • 102. Ā© 2015 Pearson Education Ltd Figure 9.UN01c ļ„Fus3
  • 103. Ā© 2015 Pearson Education Ltd Figure 9.UN01d ļ„formin
  • 104. Ā© 2015 Pearson Education Ltd Figure 9.UN02 Reception Transduction Response Relay molecules Signaling molecule Receptor Activation of cellular response 1 2 3 1 2 3
  • 105. Ā© 2015 Pearson Education Ltd Figure 9.UN03