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LECTURE PRESENTATIONS
For CAMPBELL BIOLOGY, NINTH EDITIONJane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson
2011 Pearson Education, Inc.
Lectures by
Erin Barley
Kathleen Fitzpatrick
Cell Communication
Chapter 11
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Overview: Cellular Messaging
Cell-to-cell communication is essential for bothmulticellular and unicellular organisms
Biologists have discovered some universal
mechanisms of cellular regulation
Cells most often communicate with each other
via chemical signals
For example, the fight-or-flight response is
triggered by a signaling molecule calledepinephrine
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Figure 11.1
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Concept 11.1: External signals are
converted to responses within the cell
Microbes provide a glimpse of the role of cell
signaling in the evolution of life
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Evolution of Cell Signaling
The yeast, Saccharomyces cerevisiae, has twomating types, aand
Cells of different mating types locate each othervia secreted factors specific to each type
A signal transduction pathway is a series ofsteps by which a signal on a cells surface isconverted into a specific cellular response
Signal transduction pathways convert signals ona cells surface into cellular responses
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Figure 11.2
Exchange
of mating
factors
Receptorfactor
a factorYeast cell,
mating type aYeast cell,
mating type Mating
New a/cell
1
2
3
a
a
a/
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Pathway similarities suggest that ancestralsignaling molecules evolved in prokaryotes and
were modified later in eukaryotes
The concentration of signaling molecules allows
bacteria to sense local population density
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Individual
rod-shaped
cells
Spore-forming
structure
(fruiting body)
Aggregation
in progress
Fruiting bodies
1
2
3
0.5 mm
2.5 mm
Figure 11.3
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Figure 11.3a
Individual rod-shaped cells1
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Figure 11.3b
Aggregation in progress2
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Figure 11.3c
Spore-forming structure(fruiting body)
0.5 mm
3
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Figure 11.3d
Fruiting bodies
2.5 mm
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Local and Long-Distance Signaling
Cells in a multicellular organism communicate bychemical 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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Figure 11.4Plasma membranes
Gap junctions
between animal cellsPlasmodesmata
between plant cells
(a) Cell junctions
(b) Cell-cell recognition
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In many other cases, animal cells communicateusing local regulators, messenger molecules that
travel only short distances
In long-distance signaling, plants and animals use
chemicals called hormones
The ability of a cell to respond to a signal depends
on whether or not it has a receptor specific to that
signal
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Figure 11.5
Local signaling Long-distance signaling
Target cell
Secreting
cellSecretory
vesicle
Local regulator
diffuses through
extracellular fluid.
(a) Paracrine signaling (b) Synaptic signaling
Electrical signal
along nerve cell
triggers release of
neurotransmitter.
Neurotransmitter
diffuses across
synapse.
Target cell
is stimulated.
Endocrine cellBlood
vessel
Hormone travels
in bloodstream.
Target cell
specifically
binds
hormone.
(c) Endocrine (hormonal) signaling
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Figure 11.5a
Local signaling
Target cell
Secreting
cell Secretoryvesicle
Local regulator
diffuses throughextracellular fluid.
(a) Paracrine signaling (b) Synaptic signaling
Electrical signal
along nerve cell
triggers release of
neurotransmitter.
Neurotransmitter
diffuses acrosssynapse.
Target cell
is stimulated.
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Figure 11.5b
Long-distance signaling
Endocrine cellBlood
vessel
Hormone travels
in bloodstream.
Target cell
specifically
binds
hormone.
(c) Endocrine (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 signalswent through three processes
Reception
Transduction
Response
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Animation: Overview of Cell Signaling
Fi 11 6 1
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Figure 11.6-1
Plasma membrane
EXTRACELLULARFLUID
CYTOPLASM
Reception
Receptor
Signaling
molecule
1
Figure 11 6 2
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Figure 11.6-2
Plasma membrane
EXTRACELLULARFLUID
CYTOPLASM
Reception Transduction
Receptor
Signaling
molecule
Relay molecules in a signal transduction
pathway
21
Figure 11 6 3
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Figure 11.6-3
Plasma membrane
EXTRACELLULARFLUID
CYTOPLASM
Reception Transduction Response
Receptor
Signaling
molecule
Activationof cellular
responseRelay molecules in a signal transduction
pathway
321
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Concept 11.2: Reception: A signaling
molecule binds to a receptor protein, causing
it to change shape
The binding between a signal molecule (ligand)
and receptor is highly specific 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 tospecific sites on receptor proteins that span theplasma membrane
There are three main types of membrane
receptors
G protein-coupled receptors
Receptor tyrosine kinases
Ion channel receptors
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G protein-coupled receptors (GPCRs) are thelargest family of cell-surface receptors
A GPCR 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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Figure 11 7a
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Figure 11.7a
G protein-coupled receptor
Signaling molecule binding site
Segment thatinteracts withG proteins
Figure 11 7b
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Figure 11.7b
G protein-coupled
receptor
21
3 4
Plasmamembrane
G protein(inactive)
CYTOPLASMEnzyme
Activatedreceptor
Signalingmolecule
Inactiveenzyme
Activatedenzyme
Cellular response
GDPGTP
GDPGTP
GTP
P i
GDP
GDP
Figure 11.8
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Figure 11.8
Plasmamembrane
Cholesterol
2-adrenergicreceptors
Moleculeresemblingligand
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Receptor tyrosine kinases (RTKs) aremembrane receptors that attach phosphates to
tyrosines
A receptor tyrosine kinase can trigger multiple
signal transduction pathways at once
Abnormal functioning of RTKs is associated with
many types of cancers
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Figure 11.7c
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g
Signaling
molecule (ligand)
21
3 4
Ligand-binding site
helix in themembrane
Tyrosines
CYTOPLASM Receptor tyrosine
kinase proteins
(inactive monomers)
Signaling
molecule
Dimer
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
P
P
P
P
P
P
P
P
P
P
P
P
Activated tyrosine
kinase regions
(unphosphorylated
dimer)
Fully activated
receptor tyrosine
kinase
(phosphorylated
dimer)
Activated relay
proteins
Cellular
response 1
Cellular
response 2
Inactive
relay proteins
6 ATP 6 ADP
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A ligand-gated ion channel receptor acts as agate 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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Figure 11.7d
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g
Signalingmolecule(ligand)
21 3
Gateclosed Ions
Ligand-gatedion channel receptor
Plasmamembrane
Gateopen
Cellularresponse
Gate closed
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Intracellular Receptors
Intracellular receptor proteins are found in thecytosol 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 2011 Pearson Education, Inc.
Figure 11.9-1C
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Hormone(testosterone)
Receptorprotein
Plasmamembrane
DNA
NUCLEUS
CYTOPLASM
EXTRACELLULARFLUID
Figure 11.9-2EXTRACELLULAR
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Hormone(testosterone)
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
NUCLEUS
CYTOPLASM
EXTRACELLULARFLUID
Figure 11.9-3EXTRACELLULAR
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Hormone(testosterone)
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
NUCLEUS
CYTOPLASM
EXTRACELLULARFLUID
Figure 11.9-4
H EXTRACELLULAR
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Hormone(testosterone)
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS
CYTOPLASM
EXTRACELLULARFLUID
Figure 11.9-5
H EXTRACELLULAR
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Hormone(testosterone)
Receptorprotein
Plasmamembrane
EXTRACELLULARFLUID
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
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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 fewmolecules 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 toresponse 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 toprotein, a process called phosphorylation
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Protein phosphatases remove the phosphatesfrom proteins, a process called dephosphorylation
This phosphorylation and dephosphorylation
system acts as a molecular switch, turning
activities on and off or up or down, as required
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Figure 11.10
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Receptor
Signaling molecule
Activated relay
molecule
Inactiveprotein kinase
1 Activeproteinkinase
1
Activeproteinkinase
2
Activeproteinkinase
3
Inactiveprotein kinase2
Inactiveprotein kinase
3
Inactiveprotein
Activeprotein
Cellularresponse
ATPADP
ATPADP
ATPADP
PP
PP
PP
P
P
P
P i
P i
Pi
Figure 11.10a
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Activated relaymolecule
Inactiveprotein kinase
1 Activeproteinkinase
1
Activeproteinkinase
2
Activeprotein
kinase3
Inactiveprotein kinase
2
Inactiveprotein kinase
3
Inactiveprotein
Activeprotein
ATP
ADP
ATPADP
ATP
ADP
PP
PP
PP
P
P
P i
P i
P i
P
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Small Molecules and Ions as Second
Messengers
The extracellular signal molecule (ligand) that
binds to the receptor is a pathways first
messenger
Second messengers are small, nonprotein, water-
soluble molecules or ions that spread throughout a
cell by diffusion
Second messengers participate in pathwaysinitiated by GPCRs and RTKs
Cyclic AMP and calcium ions are common second
messengers 2011 Pearson Education, Inc.
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Cyclic AMP
Cyclic AMP (cAMP)is one of the most widelyused second messengers
Adenylyl cyclase, an enzyme in the plasma
membrane, converts ATP to cAMP in response to
an extracellular signal
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Figure 11.11
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Adenylyl cyclase Phosphodiesterase
Pyrophosphate
AMP
H2O
ATP
P iP
cAMP
Figure 11.11a
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Adenylyl cyclase
Pyrophosphate
ATP
P iP
cAMP
Figure 11.11b
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Phosphodiesterase
AMP
H2O
cAMP
H2O
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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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Figure 11.12
Fi t
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G protein
First messenger(signaling moleculesuch as epinephrine)
G protein-coupled
receptor
Adenylyl
cyclase
Secondmessenger
Cellular responses
Proteinkinase A
GTP
ATP
cAMP
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Calcium Ions and Inositol Triphosphate (IP3)
Calcium ions (Ca2+) act as a second messenger inmany pathways
Calcium is an important second messenger
because cells can regulate its concentration
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Figure 11.13
EXTRACELLULAR Plasma
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Mitochondrion
EXTRACELLULARFLUID
Plasmamembrane
Ca2pump
Nucleus
CYTOSOL
Ca2pump
Ca2pump
Endoplasmicreticulum(ER)
ATP
ATP
Low [Ca2
]High [Ca2
]Key
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A signal relayed by a signal transduction pathwaymay 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
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Animation: Signal Transduction Pathways
EXTRA
Figure 11.14-1
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G protein
EXTRA-CELLULARFLUID
Signaling molecule(first messenger)
G protein-coupledreceptor
Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER)
CYTOSOL
Ca2
GTP
Figure 11.14-2
EXTRA
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G protein
EXTRA-CELLULARFLUID
Signaling molecule(first messenger)
G protein-coupledreceptor
Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER)
CYTOSOL
Ca2(second
messenger)
Ca2
GTP
Figure 11.14-3
EXTRA
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G protein
EXTRA-CELLULARFLUID
Signaling molecule(first messenger)
G protein-coupledreceptor
Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER)
CYTOSOL
Variousproteinsactivated
Cellularresponses
Ca2(second
messenger)
Ca2
GTP
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Concept 11.4: Response: Cell signaling leads
to regulation of transcription or cytoplasmic
activities
The cells response to an extracellular signal is
sometimes called theoutput response
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Nuclear and Cytoplasmic Responses
Ultimately, a signal transduction pathway leads toregulation of one or more cellular activities
The response may occur in the cytoplasm or in thenucleus
Many signaling pathways regulate the synthesis ofenzymes or other proteins, usually by turninggenes on or off in the nucleus
The final activated molecule in the signaling
pathway may function as a transcription factor
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Figure 11.15Growth factor Reception
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Receptor
p
Transduction
CYTOPLASM
Response
Inactivetranscriptionfactor
Activetranscriptionfactor
DNA
NUCLEUS mRNA
Gene
Phosphorylationcascade
P
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Other pathways regulate the activity of enzymesrather than their synthesis
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Figure 11.16
Reception
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Transduction
Response
Binding of epinephrine to G protein-coupled receptor (1 molecule)
Inactive G protein
Active G protein (102molecules)
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)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106)
Glycogen
Glucose 1-phosphate(108molecules)
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Signaling pathways can also affect theoverall behavior of a cell, for example,
changes in cell shape
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RESULTSFigure 11.17
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Wild type (with shmoos) Fus3 formin
Matingfactoractivatesreceptor.
Matingfactor
G protein-coupledreceptor
Shmoo projectionforming
Formin
G protein binds GTPand becomes activated.
2
1
3
4
5
P
P
P
P
ForminFormin
Fus3
Fus3Fus3
GDPGTP
Phosphory-lation
cascade
Microfilament
Actinsubunit
Phosphorylation cascadeactivates Fus3, which movesto plasma membrane.
Fus3 phos-phorylatesformin,activating it.
Formin initiates growth ofmicrofilaments that formthe shmoo projections.
CONCLUSION
Figure 11.17a
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Wild type (with shmoos)
Figure 11.17b
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Fus3
Figure 11.17c
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formin
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Fine-Tuning of the Response
There are four aspects of fine-tuning to considerAmplification of the signal (and thus the response)
Specificity of the response
Overall efficiency of response, enhanced by
scaffolding proteins
Termination of the signal
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Signal Amplification
Enzyme cascades amplify the cells 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 andCoordination 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-talkfurther helpthe cell coordinate incoming signals
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Figure 11.18
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Signaling
molecule
Receptor
Relaymolecules
Response 1
Cell A. Pathway leads
to a single response.
Response 2 Response 3 Response 4 Response 5
Activation
or inhibition
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.
Signaling
Figure 11.18a
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Signalingmolecule
Receptor
Relay
molecules
Response 1
Cell A. Pathway leads
to a single response.
Response 2 Response 3
Cell B. Pathway branches,
leading to two responses.
Figure 11.18b
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Response 4 Response 5
Activation
or inhibition
Cell C. Cross-talk occurs
between two pathways.Cell D. Different receptor
leads to a different
response.
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Signaling Efficiency: Scaffolding Proteinsand 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
In some cases, scaffolding proteins may also help
activate some of the relay proteins
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Figure 11.19
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Signalingmolecule
Receptor
Plasmamembrane
Scaffoldingprotein
Threedifferentproteinkinases
T i i f h Si l
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Termination of the Signal
Inactivation mechanisms are an essential aspectof cell signaling
If ligand concentration falls, fewer receptors will be
bound
Unbound receptors revert to an inactive state
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C 11 5 A i i l i l
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Concept 11.5: Apoptosis integrates multiple
cell-signaling pathways
Apoptosis is programmed or controlled cell
suicide
Components of the cell are chopped up 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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Figure 11.20
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2 m
A i i h S il W C h bditi
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Apoptosis in the Soil Worm Caenorhabditiselegans
Apoptosis is important in shaping an organism
during embryonic development
The role of apoptosis in embryonic development
was studied in Caenorhabditis elegans
In C. elegans, apoptosis results when proteins that
accelerateapoptosis override those that put the
brakeson apoptosis
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Figure 11.21
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Mitochondrion
Ced-9
protein (active)inhibitsCed-4activity
Receptorfor death-signaling
molecule
Ced-4 Ced-3
Inactive proteins
(a) No death signal
Death-signalingmolecule
Ced-9(inactive)
Cellformsblebs
ActiveCed-4
ActiveCed-3
Otherproteases
NucleasesActivationcascade
(b) Death signal
Figure 11.21a
Ced-9
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Mitochondrion
protein (active)inhibitsCed-4activity
Receptorfor death-signalingmolecule
Ced-4 Ced-3
Inactive proteins
(a) No death signal
Ced-9 Cell
Figure 11.21b
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Death-signalingmolecule
Ced 9(inactive)
Cellformsblebs
ActiveCed-4
ActiveCed-3
Otherproteases
Nucleases
Activationcascade
(b) Death signal
A t ti P th d th Si l Th t
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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 isessential for the development and maintenance of
all animals
Apoptosis may be involved in some diseases (for
example, Parkinsons and Alzheimers);interference with apoptosis may contribute to
some cancers
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Figure 11.22
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Interdigital tissue
Cells undergoingapoptosis
Space betweendigits1 mm
Figure 11.22a
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Interdigital tissue
Figure 11.22b
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Cells undergoingapoptosis
Figure 11.22c
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Space betweendigits1 mm
Figure 11.UN01
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Reception1 2 3Transduction Response
Receptor
Signalingmolecule
Relay molecules
Activation
of cellularresponse
Figure 11.UN02
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