CAMPBELL
BIOLOGYReece • Urry • Cain • Wasserman • Minorsky • Jackson
© 2014 Pearson Education, Inc.
TENTH
EDITION
CAMPBELL
BIOLOGYReece • Urry • Cain • Wasserman • Minorsky • Jackson
TENTH
EDITION
11Cell
Communication
Lecture Presentation by
Nicole Tunbridge and
Kathleen Fitzpatrick
© 2014 Pearson Education, Inc.
Cellular Messaging
Cells can signal to each other and interpret the
signals they receive from other cells and the
environment
Signals are most often chemicals
The same small set of cell signaling mechanisms
shows up in diverse species and processes
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Figure 11.1
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Figure 11.1a
Epinephrine
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Concept 11.1: External signals are converted to responses within the cell
Communication among microorganisms provides
some insight into how cells send, receive, and
respond to signals
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Evolution of Cell Signaling
The yeast, Saccharomyces cerevisiae, has two
mating types, a and
Cells of different mating types locate each other
via secreted factors specific to each type
Signal transduction pathways convert signals
received at a cell’s surface into cellular responses
The molecular details of signal transduction in
yeast and mammals are strikingly similar
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Figure 11.2-1
Yeast cell,
mating type a
Exchange
of mating
factors
Receptor α factor
a factor Yeast cell,
mating type α
a α
1
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Figure 11.2-2
Yeast cell,
mating type a
Exchange
of mating
factors
Receptor
a factor Yeast cell,
mating type α
a α
1
a α
2 Mating
α factor
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Figure 11.2-3
Yeast cell,
mating type a
Exchange
of mating
factors
Receptor
a factor Yeast cell,
mating type α
a α
1
a α
2 Mating
3 New a/ cell
a/ α
α factor
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Pathway similarities suggest that ancestral
signaling molecules that evolved in prokaryotes
and single-celled eukaryotes were adopted for use
in their multicellular descendants
Cell signaling is critical in the microbial world
A concentration of signaling molecules allows
bacteria to sense local population density in a
process called quorum sensing
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Figure 11.3
Individual
rod-shaped
cells
1
3
2
2
0.5 mm
2.5 mm
Spore-forming
structure
(fruiting body)
Fruiting bodies
Aggregation
in progress
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Figure 11.3a
Individual rod-shaped cells1
0.5 mm
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Figure 11.3b
Aggregation in progress2
0.5 mm
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Figure 11.3c
0.5 mm
Spore-forming structure
(fruiting body)
3
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Figure 11.3d
2.5 mm
Fruiting bodies
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Local and Long-Distance Signaling
Cells in a multicellular organism communicate via
signaling molecules
In local signaling, animal cells may communicate
by direct contact
Animal and plant cells have cell junctions that
directly connect the cytoplasm of adjacent cells
Signaling substances in the cytosol can pass
freely between adjacent cells
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Figure 11.4Plasma membranes Cell wall
(a) Cell junctions
(b) Cell-cell recognition
Gap junctions
between animal cellsPlasmodesmata
between plant cells
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In many other cases, animal cells communicate
using secreted messenger molecules that travel
only short distances
Growth factors, which stimulate nearby target cells
to grow and divide, are one class of such local
regulators in animals
This type of local signaling in animals is called
paracrine signaling
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Synaptic signaling occurs in the animal nervous
system when a neurotransmitter is released in
response to an electric signal
Local signaling in plants is not well understood
beyond communication between plasmodesmata
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In long-distance signaling, plants and animals use
chemicals called hormones
Hormonal signaling in animals is called endocrine
signaling; specialized cells release hormones,
which travel to target cells via the circulatory
system
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 11.5Local 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
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Figure 11.5a
Local signaling
Target cells
Secreting
cell
Secretory
vesicles
Local regulator
(a) Paracrine signaling
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Figure 11.5b
Target cell
(b) Synaptic signaling
Electrical signal triggers
release of neurotransmitter.
Neurotransmitter
diffuses across
synapse.
Local signaling
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Figure 11.5c
(c) Endocrine (hormonal) signaling
Long-distance signaling
Endocrine cell Target cell
specifically
binds
hormone.
Hormone
travels in
bloodstream.
Blood
vessel
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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
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In reception, the target cell detects a signaling
molecule that binds to a receptor protein on the
cell surface
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
In response, the transduced signal triggers a
specific response in the target cell
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Figure 11.6-1
CYTOPLASM
Plasma membrane
EXTRACELLULAR
FLUID
Receptor
Signaling
molecule
Reception1
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Figure 11.6-2
CYTOPLASM
Plasma membrane
EXTRACELLULAR
FLUID
Receptor
Signaling
molecule
Reception1 Transduction2
Relay molecules
1 2 3
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Figure 11.6-3
CYTOPLASM
Plasma membrane
EXTRACELLULAR
FLUID
Receptor
Signaling
molecule
Reception1 Transduction2
Relay molecules
1 2 3
Response3
Activation
of cellular
response
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Animation: Overview of Cell Signaling
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 greatly amplify a signal
Multistep pathways provide more opportunities for
coordination and regulation of the cellular
response
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Signal Transduction Pathways
The binding of a signaling molecule to a receptor
triggers the first step in a chain of molecular
interactions
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
Phosphorylation and dephosphorylation of
proteins is a widespread cellular mechanism for
regulating protein activity
Protein kinases transfer phosphates from ATP to
protein, a process called phosphorylation
Many relay molecules in signal transduction
pathways are protein kinases, creating a
phosphorylation cascade
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Figure 11.10
Signaling molecule
Activated relay
moleculeReceptor
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
PPP i
P
Cellular
response
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Figure 11.10a
Signaling molecule
Activated relay
moleculeReceptor
Inactive
protein kinase
1 Active
protein
kinase
1
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Figure 11.10b
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
PPP
i
ATP
ADP
PPP
i
Phosphorylation
cascade
P
P
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Figure 11.10c
Inactive
protein kinase
3 Active
protein
kinase
3
ATP
ADP
PPP
i
Pi
P
P
ATP
ADP
PP
Inactive
protein
Active
protein
Cellular
response
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Protein phosphatases rapidly remove the
phosphates from 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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Small Molecules and Ions as Second Messengers
Many signaling pathways involve second
messengers
Second messengers are small, nonprotein,
water-soluble molecules or ions that spread
throughout a cell by diffusion
Second messengers participate in pathways
initiated by GPCRs and RTKs
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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Figure 11.11
ATP cAMP AMP
PhosphodiesteraseAdenylyl cyclase
Pyrophosphate H2O
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Figure 11.11a
ATP cAMP
Adenylyl cyclase
Pyrophosphate
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Figure 11.11b
cAMP AMP
H2O
Phosphodiesterase
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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
First messenger
(signaling molecule
such as epinephrine)
G protein
Adenylyl
cyclase
G protein-coupled
receptorSecond
messenger
Cellular responses
Protein
kinase A
GTP
ATP
cAMP
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Understanding of the role of cAMP in G protein
signaling pathways helps explain how certain
microbes cause disease
The cholera bacterium, Vibrio cholerae, produces
a toxin that modifies a G protein so that it is stuck
in its active form
This modified G protein continually makes cAMP,
causing intestinal cells to secrete large amounts of
salt into the intestines
Water follows by osmosis and an untreated person
can soon die from loss of water and salt
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Calcium Ions and Inositol Triphosphate (IP3)
Calcium ions (Ca2+) act as a second messenger in
many pathways
Ca2+ can function as a second messenger
because its concentration in the cytosol is
normally much lower than the concentration
outside the cell
A small change in number of calcium ions thus
represents a relatively large percentage change in
calcium concentration
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Figure 11.13
Endoplasmic
reticulum (ER)Plasma
membrane
Mitochondrion
ATP
ATP
ATPCYTOSOL
Nucleus
Ca2+
pump
EXTRACELLULAR
FLUID
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
These two are produced by cleavage of a certain
phospholipid in the plasma membrane
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Figure 11.14-1
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
GTP
CYTOSOLG protein-coupled
receptor Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Ca2+
Nucleus
Endoplasmic
reticulum (ER)
lumen
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Figure 11.14-2
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
GTP
CYTOSOLG protein-coupled
receptor Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Ca2+
Nucleus
Endoplasmic
reticulum (ER)
lumen
Ca2+
(second
messenger)
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Figure 11.14-3
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
GTP
CYTOSOLG 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
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Animation: Signal Transduction Pathways
Concept 11.4: Response: Cell signaling leads to regulation of transcription or cytoplasmic activities
The cell’s response to an extracellular signal is
called the “output response”
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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 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 in the signaling
pathway may function as a transcription factor
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Figure 11.15
Growth factor
Receptor
Phospho-rylation
cascade
Reception
Transduction
CYTOPLASM
Inactive
transcription
factor
Activetranscriptionfactor
DNA
ResponseP
Gene
mRNANUCLEUS
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Figure 11.15a
Growth factor
Receptor
Phospho-rylation
cascade
Reception
Transduction
NUCLEUS
CYTOPLASM
Inactive
transcription
factor
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Figure 11.15b
NUCLEUS
CYTOPLASM
Phospho-rylation
cascade Transduction
Inactive
transcription
factor
Active
transcription
factor Response
DNA
P
Gene
mRNA
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Other pathways regulate the activity of enzymes
rather than their synthesis
For example, a signal could cause opening or
closing of an ion channel in the plasma
membrane, or a change in cell metabolism
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Figure 11.16
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 phosphorylaseGlycogen
Response
Glucose 1-phosphate
(108 molecules)
Binding of epinephrine to G protein-coupled
receptor
(1 molecule)
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Figure 11.16a
Reception
Glycogen
Response
Glucose 1-phosphate
(108 molecules)
Binding of epinephrine to G protein-coupled
receptor
(1 molecule)
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Figure 11.16b
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)
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Figure 11.16c
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
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Signaling pathways can also affect the overall
behavior of a cell, for example, a signal could lead
to cell division
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Regulation of the Response
A response to a signal may not be simply “on” or
“off”
There are four aspects of signal regulation to
consider
Amplification 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 cell’s response to
the signal
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
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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Figure 11.17
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
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Figure 11.17a
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.
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Figure 11.17b
Response 4 Response 5
Cell C: Cross-talk
occurs between two
pathways.
Cell D: Different
receptor leads to a
different response.
Activation
or inhibition
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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
In some cases, scaffolding proteins may also help
activate some of the relay proteins
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Figure 11.18
Signaling
molecule
Receptor
Scaffolding
protein
Plasma
membrane
Three
different
protein
kinases
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Termination of the Signal
Inactivation mechanisms are an essential aspect
of cell signaling
If ligand concentration falls, fewer receptors will be
bound
Unbound receptors revert to an inactive state