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CHAPTER 11:
CELL
COMMUNICATION
Overview: The Cellular Internet
• Cell-to-cell communication is essential for
multicellular organisms
• Biologists have discovered some universal
mechanisms of cellular regulation
– Evidence of evolution
• The combined effects of multiple signals
determine cell response
– Ex- dilation of blood vessels is controlled by
multiple molecules
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
• 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
– Quorum sensing (Bonnie Bassler)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-3
1 Individual rodshaped cells
2 Aggregation in
process
0.5 mm
3 Spore-forming
structure
(fruiting body)
Fruiting bodies
Cell Signaling
Animal cells communicate by:
• Direct contact (gap junctions)
• Secreting local regulators
(growth factors,
neurotransmitters)
• Long distance (hormones)
Local regulators (animals): messenger molecules that travel short
distances (this process is not well understood in plants)
Examples- growth factors, neurotransmitters
Local signaling
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Target cell
Secreting
cell
Local regulator
diffuses through
extracellular fluid
(a) Paracrine signaling
Neurotransmitter
diffuses across
synapse
Secretory
vesicle
Target cell
is stimulated
(b) Synaptic signaling
Long-distance signaling
•In long-distance signaling,
plants and animals use
chemicals called hormones
•Animals- endocrine system
•Insulin- regulates sugar
levels
•Plants- plant growth regulators
(factors)
•Ethylene- fruit ripening,
regulates growth
•(Some nerve signals are
considered long-distance)
Endocrine cell
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
(c) Hormonal signaling
3 Stages of Cell Signaling:
1. Reception: Detection of a signal molecule
(ligand) coming from outside the cell
2. Transduction: Convert signal to a form that can
bring about a cellular response
3. Response: Cellular response to the signal
molecule
Reception
Transduction
Response
1. Reception
 Binding between signal molecule (ligand) +
receptor is highly specific.
 Types of Receptors:
a) Plasma membrane receptor
 water-soluble ligands
b) Intracellular receptors (cytoplasm, nucleus)

hydrophobic or small ligands

Eg. testosterone or nitric oxide (NO)
 Ligand binds to receptor protein  protein
changes SHAPE  initiates transduction signal
Receptors
• Three main types of membrane receptors:
– G protein-coupled receptors
– Tyrosine kinase receptors
– Ligand-gated ion channel receptors
• Intracellular receptors- found in the cytoplasm
or nucleus
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• A G protein-coupled receptor is a plasma
membrane receptor that works with the help of a
G protein
Signaling-molecule binding site
Segment that
interacts with
G proteins
• The G protein acts as an on/off switch:
– GDP is bound to G protein, G protein is inactive
– GTP is bound to G protein, G protein is active
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-7b
G-Protein-Coupled Receptor
Plasma
membrane
G protein-coupled
receptor
Activated
receptor
Signaling molecule
GDP
CYTOPLASM
GDP
Enzyme
G protein
(inactive)
GTP
2
1
Activated
enzyme
GTP
GDP
Pi
Cellular response
3
4
G protein receptor
Inactive
enzyme
• Tyrosine kinase receptors attach phosphates to
tyrosines; Can trigger multiple signal transduction
pathways at once
Ligand-binding site
Signaling
molecule (ligand)
Signaling
molecule
 Helix
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
CYTOPLASM
Dimer
Activated relay
proteins
Tyr
Tyr
Tyr
Tyr
P Tyr
P Tyr
Tyr
Tyr
P
6 ATP
Activated tyrosine
kinase regions
6 ADP
Tyr
Tyr
P Tyr
Tyr
P
Tyr
P Tyr
P Tyr
Tyr
P
P
P
P
Tyr P
Tyr
Fully activated receptor
tyrosine kinase
Inactive
relay proteins
Cellular
response 1
Cellular
response 2
• 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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1 Signaling
molecule
(ligand)
Gate
closed
Ligand-gated
ion channel receptor
2
Ions
Plasma
membrane
Gate open
Cellular
response
3
Gate closed
Intracellular Receptors
• Small or hydrophobic chemical messengers can
readily cross the membrane and activate
receptors inside the cell
– Examples- steroid and thyroid hormones of
animals, NO (nitric oxide)
• An activated hormone-receptor complex can act
as a transcription factor, turning on specific
genes
– These receptors also complete the
“transduction” step
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-8-1
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-2
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-3
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-4
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
Fig. 11-8-5
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
Intracellular
Receptors
2. Transduction
• Cascades of molecular interactions relay
signals from receptors  target molecules
• Protein kinase: enzyme that
phosphorylates and activates proteins at
next level
– transfer phosphates from ATP to protein, a
process called phosphorylation
• Phosphorylation cascade: enhance and
amplify signal
• 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-9
Signaling molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
ADP
Pi
P
Active
protein
kinase
2
PP
Inactive
protein kinase
3
Pi
ATP
ADP
Active
protein
kinase
3
PP
Inactive
protein
P
ATP
P
ADP
Pi
PP
Active
protein
Cellular
response
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Adenylyl cyclase
Phosphodiesterase
Pyrophosphate
P
ATP
Pi
cAMP
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
AMP
Fig. 11-11
First messenger
Adenylyl
cyclase
G protein
G protein-coupled
receptor
GTP
ATP
cAMP
Second
messenger
Protein
kinase A
Cellular responses
EXTRACELLULAR
FLUID
Calcium Ions
• Calcium ions
act as a second
messenger in many
pathways
Ca2+ pump
(Ca2+)
– More widely used
than cAMP
• Calcium is an
important second
messenger because
cells can regulate its
concentration
Plasma
membrane
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
Endoplasmic
reticulum (ER)
ATP
Key
High [Ca2+]
Low [Ca2+]
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Ca2+
pump
• A signal relayed by a signal transduction
pathway may trigger an increase in calcium in
the cytosol
– Phospholipase C cleaves the plasma
membrane phospholipid PIP2 into DAG and IP3.
• Additional second messengers:
– Inositol triphosphate (IP3)
– Diacylglycerol (DAG)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-13-3
EXTRACELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
PIP2
Phospholipase C
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Various
proteins
activated
Ca2+
Ca2+
(second
messenger)
Cellular
responses
3. Response
•
Regulate protein synthesis
by turning on/off genes in
nucleus (gene expression)
•
Regulate activity of proteins
in cytoplasm
• Other pathways regulate the activity of enzymes
Reception
Binding of epinephrine to G protein-coupled receptor (1 molecule)
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)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106)
Response
Glycogen
Glucose-1-phosphate
(108 molecules)
• Signaling pathways can also affect the physical
characteristics of a cell, for example, cell shape
RESULTS
Wild-type (shmoos)
∆Fus3
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∆formin
Fig. 11-16b
CONCLUSION
1
Mating
factor G protein-coupled
receptor
Shmoo projection
forming
Formin
P
Fus3
GTP
GDP
Phosphorylation
cascade
2
Actin
subunit
P
Formin
Formin
P
4
Fus3
Fus3
P
Microfilament
5
3
What a great connection from ch 11 back to ch 6… hint, hint…
Fine-Tuning of the Response
• Multistep pathways have two important benefits:
– Amplifying the signal (and thus the response)
– Provide different points at which the response
can be regulated
• Contributes to the specificity of the response
• The response can also ultimately be ended
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
– Small number of epinephrine molecules can
lead to the release of hundreds of millions of
glucose molecules from glycogen
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
The Specificity of Cell Signaling
and Coordination of the Response
• Different kinds of cells have
different collections of proteins
– allows cells to detect and
respond to different signals
– 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
Signaling
molecule
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.
Activation
or inhibition
Response 4
Cell C. Cross-talk occurs
between two pathways.
Response 5
Cell D. Different receptor
leads to a different response.
Signaling Efficiency: Scaffolding Proteins and Signaling Complexes
• Scaffolding proteins are large relay proteins to
which other relay proteins are attached
– can increase signal transduction efficiency by grouping
together different proteins involved in the same pathway
Signaling
molecule
Plasma
membrane
Receptor
Three
different
protein
kinases
Scaffolding
protein
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
– Each molecular chain in the cascade lasts only
a short time
• GTPase hydrolyzes GTP
• Phosphodiesterase converts cAMP to AMP
• Protein phosphatases inactivate kinases
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Concept 11.5: Apoptosis (programmed cell death)
integrates multiple cell-signaling pathways
• Apoptosis is programmed (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
Blebs
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• ced-9 = gene
Ced-9
protein (active)
inhibits Ced-4
activity
• Ced-9 = protein
• Inhibitory signal (from
Ced-9) should look like:
Mitochondrion
Ced-4 Ced-3
Receptor
for deathsignaling
molecule
Inactive proteins
(a) No death signal
Ced-9
(inactive)
Cell
forms
blebs
Deathsignaling
molecule
Active Active
Ced-4 Ced-3
Activation
cascade
(b) Death signal
Other
proteases
Nucleases
• Built-in cell suicide mechanisms are essential
to development and maintenance in organisms.
Interdigital tissue
1 mm
• Apoptosis may be involved in some diseases
(for example, Parkinson’s and Alzheimer’s);
interference with apoptosis contributes to some
cancers
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
You should now be able to:
1. Describe a ligand-receptor interaction and state how such
interactions initiate a signal-transduction system
2. Compare/contrast ligand-gated ion channels, G proteincoupled receptors, & tyrosine kinase receptors
3. List 2 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
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