Cell Communication - Houston Community College
Transcript of Cell Communication - Houston Community College
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Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
PowerPoint® Lecture Presentations for
BiologyEighth Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp
Chapter 11
Cell Communication
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Overview: The Cellular Internet
• Cell-to-cell communication is essential for multicellular organisms
• Biologists have discovered some universal mechanisms of cellular regulation
• The combined effects of multiple signals determine cell response
• For example, the dilation of blood vessels is controlled by multiple molecules
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Fig. 11-1
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Concepts in this Chapter1. External signals are converted to responses
within the cell
2. Reception: A signaling molecule binds to a receptor protein, causing it to change shape
3. Transductions: Cascades of molecular interactions realy signals from receptors to target molecules in the cell
4. Response; Cell signaling leads to regulation of transcription or cytoplasmic activities
5. Apoptosis (programmed cell death) integrates multiple cell-signaling pathways
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CONCEPT 11.1: EXTERNAL SIGNALS ARE
CONVERTED TO RESPONSES WITHIN THE CELL
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Concept 11.1: External signals are converted to responses within the cell
• Microbes are a window on the role of cell signaling in the evolution of life
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Fig. 11-2
Receptorα factor
a factor
a α
αa
Exchangeof matingfactors
Yeast cell,mating type a
Yeast cell,mating type α
Mating
New a/αcell
a/α
1
2
3
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Evolution of Cell Signaling
• A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response
• Signal transduction pathways convert signals on a cell’s surface into cellular responses
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• Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes
• The concentration of signaling molecules allows bacteria to detect population density
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Evolution of Cell Signaling
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Fig. 11-3
Individual rod-shaped cells
Spore-formingstructure(fruiting body)
Aggregation inprocess
Fruiting bodies
0.5 mm
1
3
2
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Local and Long-Distance Signaling
• Cells in a multicellular organism communicate by chemical messengers
• Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells
• In local signaling, animal cells may communicate by direct contact, or cell-cell recognition
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Fig. 11-4Plasma membranes
Gap junctionsbetween animal cells
(a) Cell junctions
Plasmodesmatabetween plant cells
(b) Cell-cell recognition
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• In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances
– Growth factors
– neurotransmitters
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Local and Long-Distance Signaling
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Fig. 11-5ab
Local signaling
Target cell
Secretoryvesicle
Secretingcell
Local regulatordiffuses throughextracellular fluid
(a) Paracrine signaling (b) Synaptic signaling
Target cellis stimulated
Neurotransmitterdiffuses across
synapse
Electrical signalalong nerve celltriggers release ofneurotransmitter
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• In long-distance signaling, plants and animals use chemicals called hormones
– Endocrine
– Signal in nervous system
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Local and Long-Distance Signaling
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Fig. 11-5c
Long-distance signaling
Endocrine cell Bloodvessel
Hormone travelsin bloodstreamto target cells
Targetcell
(c) Hormonal signaling
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The Three Stages of Cell Signaling: A Preview
• Earl W. Sutherland discovered how the hormone epinephrine acts on cells
• Sutherland suggested that cells receiving signals went through three processes:– Reception– Transduction– Response
Animation: Overview of Cell Signaling
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Fig. 11-6-1
Reception1
EXTRACELLULARFLUID
Signalingmolecule
Plasma membraneCYTOPLASM
1
Receptor
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Fig. 11-6-2
1
EXTRACELLULARFLUID
Signalingmolecule
Plasma membraneCYTOPLASM
Transduction2
Relay molecules in a signal transduction pathway
Reception1
Receptor
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Fig. 11-6-3
EXTRACELLULARFLUID
Plasma membraneCYTOPLASM
Receptor
Signalingmolecule
Relay molecules in a signal transduction pathway
Activationof cellularresponse
Transduction Response2 3Reception1
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CONCEPT 11.2: RECEPTION: A SIGNAL MOLECULE BINDS TO A
RECEPTOR PROTEIN, CAUSING IT TO CHANGE SHAPE
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Concept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shape
• The binding between a signal molecule and receptor is highly specific
– Signal molecule- ligand
• A shape change in a receptor is often the initial transduction of the signal
• Most signal receptors are plasma membrane proteins
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Receptors in the Plasma Membrane
• Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane
• There are three main types of membrane receptors:– G protein-coupled receptors– Receptor tyrosine kinases– Ion channel receptors
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• A G protein-coupled receptor is a plasma membrane receptor that works with the help of a G protein
• The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive
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Receptors in the Plasma Membrane
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Fig. 11-7a
Signaling-molecule binding site
Segment thatinteracts withG proteins
G protein-coupled receptor
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Fig. 11-7b
G protein-coupledreceptor
Plasmamembrane
EnzymeG protein(inactive)
GDP
CYTOPLASM
Activatedenzyme
GTP
Cellular response
GDPP i
Activatedreceptor
GDP GTP
Signaling moleculeInactiveenzyme
1 2
3 4
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• Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines
– Kinase- an enzyme that catalyzes the transfer of phosphate group
• A receptor tyrosine kinase can trigger multiple signal transduction pathways at once
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Receptors in the Plasma Membrane
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Fig. 11-7c
Signalingmolecule (ligand)
Ligand-binding site
α Helix
TyrosinesTyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosinekinase proteins
CYTOPLASM
Signalingmolecule
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Dimer
Activated relayproteins
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
PPP
PPP
Cellularresponse 1
Cellularresponse 2
Inactiverelay proteins
Activated tyrosinekinase regions
Fully activated receptortyrosine kinase
6 6 ADPATP
Tyr
Tyr
Tyr
TyrTyr
Tyr
Tyr
Tyr
Tyr
TyrTyr
Tyr
PPP
PPP
1 2
3 4
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• A ligand-gated ion channel receptor acts as a gate when the receptor changes shape
• 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
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Receptors in the Plasma Membrane
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Fig. 11-7dSignalingmolecule(ligand)
Gateclosed Ions
Ligand-gatedion channel receptor
Plasmamembrane
Gate open
Cellularresponse
Gate closed3
2
1
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Intracellular Receptors
• Some receptor proteins are intracellular, found in the cytosol or nucleus of target cells
• Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors
• Examples of hydrophobic messengers are the steroid and thyroid hormones of animals
• An activated hormone-receptor complex can act as a transcription factor, turning on specific genes
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Fig. 11-8-1Hormone(testosterone)
Receptorprotein
Plasmamembrane
EXTRACELLULARFLUID
DNA
NUCLEUS
CYTOPLASM
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Fig. 11-8-2
Receptorprotein
Hormone(testosterone)
EXTRACELLULARFLUID
Plasmamembrane
Hormone-receptorcomplex
DNA
NUCLEUS
CYTOPLASM
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Fig. 11-8-3Hormone(testosterone)
EXTRACELLULARFLUID
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
NUCLEUS
CYTOPLASM
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Fig. 11-8-4Hormone(testosterone)
EXTRACELLULARFLUID
PlasmamembraneReceptor
protein
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS
CYTOPLASM
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Fig. 11-8-5Hormone(testosterone)
EXTRACELLULARFLUID
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS New protein
CYTOPLASM
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CONCEPT 11.3: TRANSDUCTION: CASCADES
OF MOLECULAR INTERACTIONS RELAY
SIGNALS FROM RECEPTORS TO TARGET MOLECULES IN
THE CELL
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Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell
• Signal transduction usually involves multiple steps
• Multistep pathways can amplify a signal: A few molecules can produce a large cellular response
• Multistep pathways provide more opportunities for coordination and regulation of the cellular response
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Signal Transduction Pathways
• The molecules that relay a signal from receptor to response are mostly proteins
• Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated
• At each step, the signal is transduced into a different form, usually a shape change in a protein
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Protein Phosphorylation and Dephosphorylation
• In many pathways, the signal is transmitted by a cascade of protein phosphorylations
• Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation
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• Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation
• This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off
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Protein Phosphorylation and Dephosphorylation
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Fig. 11-9
Signaling molecule
ReceptorActivated relaymolecule
Inactiveprotein kinase
1 Activeproteinkinase
1
Inactiveprotein kinase
2ATP
ADP Activeproteinkinase
2
P
PPP
Inactiveprotein kinase
3ATP
ADP Activeproteinkinase
3
P
PPP
i
ATPADP P
ActiveproteinPP
Pi
Inactiveprotein
Cellularresponse
i
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Small Molecules and Ions as Second Messengers
• The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger”
• Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion
• Second messengers participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases
• Cyclic AMP and calcium ions are common second messengers
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Cyclic AMP
• Cyclic AMP (cAMP) is one of the most widely used second messengers
• Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal
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Adenylyl cyclase
Fig. 11-10
PyrophosphateP P i
ATP cAMP
Phosphodiesterase
AMP
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• Many signal molecules trigger formation of cAMP
• Other components of cAMP pathways are G proteins, G protein-coupled receptors, and protein kinases
• cAMP usually activates protein kinase A, which phosphorylates various other proteins
• Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase
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Cyclic AMP
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First messengerFig. 11-11
G proteinAdenylylcyclase
GTP
ATPcAMP Second
messenger
Proteinkinase A
G protein-coupledreceptor
Cellular responses
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• Some microbes can cause disease by disrupting G-protein signaling pathways– Cholera toxin modifies a g protein that
regulates salt and water secretion
– Unable to hydrolyze GTP to GDP
– G protein stuck in active form, continuously
stimulating adenylate cyclase to make cAMP
– High cAMP leads to large secretion of water and salt, diarrhea, death
• In Nature, Ted Abel and colleagues now report that sleep deprivation attenuates cAMP signaling in the hippocampus, which blocks long-term potentiation (LTP) and memory formation in mice.
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Cyclic AMP
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Calcium Ions and Inositol Triphosphate (IP3)
• Calcium ions (Ca2+) act as a second messenger in many pathways
• Calcium is an important second messenger because cells can regulate its concentration
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EXTRACELLULARFLUID
Fig. 11-12
ATP
Nucleus
Mitochondrion
Ca2+ pump
Plasmamembrane
CYTOSOL
Ca2+
pumpEndoplasmicreticulum (ER)
Ca2+
pumpATP
Key
High [Ca2+]Low [Ca2+]
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• A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol
• Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers
Animation: Signal Transduction Pathways
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Fig. 11-13-1
EXTRA-CELLULARFLUID
Signaling molecule(first messenger)
G protein
GTP
G protein-coupledreceptor Phospholipase C PIP2
IP3
DAG
(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER) Ca2+
CYTOSOL
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Fig. 11-13-2
G protein
EXTRA-CELLULARFLUID
Signaling molecule(first messenger)
G protein-coupledreceptor Phospholipase C PIP2
DAG
IP3(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER) Ca2+
CYTOSOL
Ca2+
(secondmessenger)
GTP
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Fig. 11-13-3
G protein
EXTRA-CELLULARFLUID
Signaling molecule(first messenger)
G protein-coupledreceptor Phospholipase C PIP2
DAG
IP3(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER) Ca2+
CYTOSOL
Variousproteinsactivated
Cellularresponses
Ca2+
(secondmessenger)
GTP
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CONCEPT 11.4: RESPONSE: CELL SIGNALING LEADS TO REGULATION OF
TRANSCRIPTION OR CYTOPLASMIC ACTIVITIES
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Concept 11.4: Response: Cell signaling leads to regulation of transcription or cytoplasmic activities
• The cell’s response to an extracellular signal is sometimes called the “output response”
• Signaling pathway benefits
– Amplify signal
– Provide regulation points
– Allow cells to respond specifically based on proteins within cell
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Nuclear and Cytoplasmic Responses
• Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities
• The response may occur in the cytoplasm or may involve action in the nucleus
• Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus
• The final activated molecule may function as a transcription factor
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Fig. 11-14Growth factor
Receptor
Phosphorylation
cascade
Reception
Transduction
Activetranscriptionfactor Response
P
Inactivetranscriptionfactor
CYTOPLASM
DNA
NUCLEUS mRNA
Gene
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• Other pathways regulate the activity of enzymes
• Stimulation of glycogen breakdown
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Fig. 11-15
Reception
Transduction
Response
Binding of epinephrine to G protein-coupled receptor (1 molecule)
Inactive G protein
Active G protein (102 molecules)
Inactive adenylyl cyclaseActive adenylyl cyclase (102)
ATPCyclic AMP (104)
Inactive protein kinase AActive protein kinase A (104)
Inactive phosphorylase kinaseActive phosphorylase kinase (105)
Inactive glycogen phosphorylaseActive glycogen phosphorylase (106)
GlycogenGlucose-1-phosphate
(108 molecules)
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• Signaling pathways can also affect the physical characteristics of a cell, for example, cell shape
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Fig. 11-16a
RESULTS
Wild-type (shmoos) ∆Fus3 ∆formin
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Fine-Tuning of the Response
• Multistep pathways have two important benefits:– Amplifying the signal (and thus the response)– Contributing to the specificity of the response
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Signal Amplification
• Enzyme cascades amplify the cell’s response
• At each step, the number of activated products is much greater than in the preceding step
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The Specificity of Cell Signaling and Coordination of the Response
• Different kinds of cells have different collections of proteins
• These different proteins allow cells to detect and respond to different signals
• Even the same signal can have different effects in cells with different proteins and pathways
• Pathway branching and “cross-talk” further help the cell coordinate incoming signals
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Fig. 11-17a
Signalingmolecule
Receptor
Relaymolecules
Response 1
Cell A. Pathway leadsto a single response.
Cell B. Pathway branches,leading to two responses.
Response 2 Response 3
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Fig. 11-17b
Response 4 Response 5
Activationor inhibition
Cell C. Cross-talk occursbetween two pathways.
Cell D. Different receptorleads to a different response.
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Signaling Efficiency: Scaffolding Proteins and Signaling Complexes
• Scaffolding proteins are large relay proteins to which other relay proteins are attached
• Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway
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Fig. 11-18
Signalingmolecule
Receptor
Scaffoldingprotein
Plasmamembrane
Threedifferentproteinkinases
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Termination of the Signal
• Inactivation mechanisms are an essential aspect of cell signaling
• When signal molecules leave the receptor, the receptor reverts to its inactive state
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CONCEPT 11.5: APOPTOSIS (PROGRAMMED CELL DEATH) INTEGRATES
MULTIPLE CELL-SIGNALING PATHWAYS
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Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathways
• Apoptosis is programmed or controlled cell suicide
• A cell is chopped and packaged into vesicles that are digested by scavenger cells
• Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells
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Fig. 11-19
2 µm
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Apoptosis in the Soil Worm Caenorhabditis elegans
• Apoptosis is important in shaping an organism during embryonic development
• The role of apoptosis in embryonic development was first studied in Caenorhabditis elegans
• In C. elegans, apoptosis results when specific proteins that “accelerate” apoptosis override those that “put the brakes” on apoptosis
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Fig. 11-20a
Ced-9protein (active)inhibits Ced-4activity
Mitochondrion
Ced-4 Ced-3Receptorfor death-signalingmolecule
Inactive proteins
(a) No death signal
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Fig. 11-20b
(b) Death signal
Death-signalingmolecule
Ced-9(inactive)
Cellformsblebs
ActiveCed-4
ActiveCed-3
Activationcascade
Otherproteases
Nucleases
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Apoptotic Pathways and the Signals That Trigger Them
• Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis
• Apoptosis can be triggered by:– An extracellular death-signaling ligand– DNA damage in the nucleus– Protein misfolding in the endoplasmic
reticulum
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• Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals
• Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers
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Apoptotic Pathways and the Signals That Trigger Them
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Fig. 11-21
Interdigital tissue 1 mm
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You should now be able to:
1. Describe the nature of a ligand-receptor interaction and state how such interactions initiate a signal-transduction system
2. Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligand-gated ion channels
3. List two advantages of a multistep pathway in the transduction stage of cell signaling
4. Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell
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5. Define the term second messenger; briefly describe the role of these molecules in signaling pathways
6. Explain why different types of cells may respond differently to the same signal molecule
7. Describe the role of apoptosis in normal development and degenerative disease in vertebrates
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