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Symphony of communication
LECTURE PRESENTATIONS
For CAMPBELL BIOLOGY, NINTH EDITION
Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson
Chapter 11
Cell Communication
Lectures by
Erin Barley
Kathleen Fitzpatrick
© 2011 Pearson Education, Inc.
Overview: Cellular Messaging
• Cell-to-cell communication is essential for both
multicellular 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 called
epinephrine
© 2011 Pearson Education, Inc.
Cellular
communication
Contact
Types of signaling
Local
Paracrine
Synaptic
Long-distance
Endocrine
system: via
hormones
Neuronal: via
elctricity
Cellular
communication
Contact
Types of signaling
Local
Paracrine
Synaptic
Long-distance
Endocrine
system: via
hormones
Neuronal: via
elctricity
Cellular
communication
Contact
Types of signaling
Local
Paracrine
Synaptic
Long-distance
Endocrine
system: via
hormones
Neuronal: via
elctricity
Cellular
communication
Contact
Types of signaling
Local
Paracrine
Synaptic
Long-distance
Endocrine
system: via
hormones
Neuronal: via
electricity
Figure 11.1
• Concept 11.1: External signals are converted
to responses within the cell
• Concept 11.2: Reception: A signaling
molecule binds to a receptor protein, causing
it to change shape
• Concept 11.3: Transduction: Cascades of
molecular interactions relay signals from
receptors to target molecules in the
cellConcept
• 11.4: Response: Cell signaling leads to
regulation of transcription or cytoplasmic
activities
• Concept 11.5: Apoptosis integrates multiple cell-signaling
pathways
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
© 2011 Pearson Education, Inc.
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
• 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
© 2011 Pearson Education, Inc.
 factor
Receptor
Communicati
on between
mating yeast
cells
How can
this be
analogized
to
people?
1 Exchange
of mating
factors

a
a factor
Yeast cell,
Yeast cell,
mating type a
mating type 
2 Mating

a
3 New a/ cell
a/
• How could we find out how long ago cell
communication evolved?
© 2011 Pearson Education, Inc.
• How could we find out how long ago cell
communication evolved?
• See if similar mechanisms are present in bacteria
and recently developed organisms like people.
© 2011 Pearson Education, Inc.
The concentration of
signaling molecules
allows bacteria to sense
local population density
1 Individual
rod-shaped
cells
2 Aggregation
in progress
0.5 mm
3 Spore-forming
structure
(fruiting body)
2.5 mm
Fruiting bodies
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
© 2011 Pearson Education, Inc.
Figure 11.4
Plasma membranes
Gap junctions
between animal cells
(a) Cell junctions
(b) Cell-cell recognition
Plasmodesmata
between plant cells
Figure 11.5a
Local signaling
Target cell
Secreting
cell
Secretory
vesicle
Local regulator
diffuses through
extracellular fluid.
(a) Paracrine signaling using local regulators
Electrical signal
along nerve cell
triggers release of
neurotransmitter.
Neurotransmitter
diffuses across
synapse.
Target cell
is stimulated.
(b) Synaptic signaling with
neurotransmitters
Figure 11.5b
Long-distance signaling
Endocrine cell
Blood
vessel
Hormone travels
in bloodstream.
Target cell
specifically
binds
hormone.
(c) Endocrine (hormonal) signaling
The Three Stages of Cell Signaling:
1. Reception
2. Transduction
3. Response
© 2011 Pearson Education, Inc.
Animation: Overview of Cell Signaling
Right-click slide / select “Play”
© 2011 Pearson Education, Inc.
Figure 11.6-1
EXTRACELLULAR
FLUID
1 Reception
Receptor
Signaling
molecule
CYTOPLASM
Plasma membrane
Figure 11.6-2
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
Receptor
Relay molecules in a signal transduction
pathway
Signaling
molecule
Figure 11.6-3
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
3 Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction
pathway
Signaling
molecule
Concept 11.2: Reception: A signaling
molecule binds to a receptor protein, causing
it to change shape
© 2011 Pearson Education, Inc.
Receptors in the Plasma Membrane
• There are three main types of membrane
receptors
1. G protein-coupled receptors
2. Receptor tyrosine kinases
3. Ion channel receptors
© 2011 Pearson Education, Inc.
• G protein-coupled receptors (GPCRs) are the largest family of cellsurface receptors
The G protein acts as an on/off switch: If GDP is bound to the G
protein, the G protein is inactive
Signaling molecule binding site
Segment that
interacts with
G proteins
G protein-coupled receptor
Figure 11.7b
Note: the enzyme is activated
by shape change
G protein-coupled
receptor
Plasma
membrane
Activated
receptor
1
Inactive
enzyme
GTP
GDP
GDP
CYTOPLASM
Signaling
molecule
Enzyme
G protein
(inactive)
2
GDP
GTP
Activated
enzyme
GTP
GDP
Pi
3
Cellular response
4
Figure 11.8:
The sturcutre of a G Protien-Coupled Receptor
2-adrenergic
receptors
Plasma
membrane
Cholesterol
Molecule
resembling
ligand
2. Receptor tyrosine kinase
Signaling
molecule (ligand)
Ligand-binding site
 helix in the
membrane
Signaling
molecule
Tyrosines
CYTOPLASM
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
1
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Dimer
2
Activated relay
proteins
3
Tyr
Tyr
P Tyr
Tyr P
P Tyr
Tyr P
Tyr
Tyr
P Tyr
Tyr P
P Tyr
Tyr P
Tyr
Tyr
P Tyr
Tyr P
P Tyr
Tyr P
6
ATP
Activated tyrosine
kinase regions
(unphosphorylated
dimer)
6 ADP
Fully activated
receptor tyrosine
kinase
(phosphorylated
dimer)
4
Inactive
relay proteins
Cellular
response 1
Cellular
response 2
• Receptor tyrosine kinases (RTKs) are
membrane receptors that attach phosphates to
tyrosines
– Benefit: A receptor tyrosine kinase can trigger
multiple signal transduction pathways at once
• Tidbit: Abnormal functioning of RTKs is associated
with many types of cancers
© 2011 Pearson Education, Inc.
Figure 11.7d
A ligand-gated ion channel receptor acts as a gate when the
receptor changes shape
When a ligand binds to the receptor, the gate allows specific
ions, such as Na+ or Ca2+, through a channel in the receptor
1
Signaling
molecule
(ligand)
3
2
Gate
closed
Ions
Plasma
Ligand-gated
membrane
ion channel receptor
Gate closed
Gate
open
Cellular
response
Intracellular Receptors
• Intracellular receptor proteins are 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 (lipid soluble) hormones of
animals
© 2011 Pearson Education, Inc.
Figure 11.9-1
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
DNA
NUCLEUS
CYTOPLASM
Figure 11.9-2
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
NUCLEUS
CYTOPLASM
Figure 11.9-3
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
NUCLEUS
CYTOPLASM
Figure 11.9-4
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
Figure 11.9-5
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
Concept 11.3: Transduction: Cascades of
molecular interactions relay signals from
receptors to target molecules in the cell
• Signal transduction usually involves multiple steps
– What are some benefits of a multistep pathway
a.k.a. cascade?
© 2011 Pearson Education, Inc.
Concept 11.3: Transduction: Cascades of
molecular interactions relay signals from
receptors to target molecules in the cell
• Signal transduction usually involves multiple steps,
a.k.a. cascade?
– Benefit 1: can amplify a signal: (A few molecules
can produce a large cellular response)
– Benefit 2: provide more opportunities for
coordination and regulation of the cellular response
© 2011 Pearson Education, Inc.
Protein Phosphorylation and
Dephosphorylation is the cascade’s signal
• Protein kinases transfer phosphates from ATP to
protein, a process called phosphorylation
• 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 or up or down, as required
© 2011 Pearson Education, Inc.
Figure 11.10
Signaling molecule
Receptor
“upstream”/”downstream”
regulation
Activated relay
molecule
Inactive
protein kinase
1
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
ADP
P
Active
protein
kinase
2
PP
Pi
Inactive
protein kinase
3
ATP
ADP
Pi
Active
protein
kinase
3
PP
Inactive
protein
P
ATP
P
ADP
PP
Pi
Active
protein
Cellular
response
Small Molecules and Ions as Second
Messengers
• The extracellular signal molecule (ligand) that
binds to the receptor is a pathway’s “first
messenger”
• Second messengers are small, nonprotein, watersoluble molecules or ions that spread throughout a
cell by diffusion
– Cyclic AMP and calcium ions are common second
messengers
© 2011 Pearson Education, Inc.
Figure 11.11
What other organic molecule do
cAMP resemble?
Adenylyl cyclase
Phosphodiesterase
H2O
Pyrophosphate
P Pi
ATP
cAMP
Why?
AMP
Figure 11.12
First messenger
(signaling molecule
such as epinephrine)
Adenylyl
cyclase
G protein
G protein-coupled
receptor
GTP
ATP
cAMP
Second
messenger
Protein
kinase A
Cellular responses
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
© 2011 Pearson Education, Inc.
Figure 11.13
EXTRACELLULAR
FLUID
Plasma
membrane
Ca2
pump
Mitochondrion
ATP
Nucleus
CYTOSOL
Ca2
pump
ATP
Key
High [Ca2 ]
Ca2
pump
Endoplasmic
reticulum
(ER)
Low [Ca2 ]
Animation: Signal Transduction Pathways
Right-click slide / select “Play”
© 2011 Pearson Education, Inc.
Figure 11.14-1: Calcium and IP3 in signaling pathways
EXTRACELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
Phospholipase C
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Ca2
Figure 11.14-2
EXTRACELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
Phospholipase C
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Ca2
Ca2
(second
messenger)
Figure 11.14-3
EXTRACELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
Phospholipase C
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Various
proteins
activated
Ca2
Ca2
(second
messenger)
Cellular
responses
Concept 11.4: Response: Cell signaling leads to
regulation of transcription or cytoplasmic
activities
• The final activated molecule in the signaling
pathway may have a response in the cytoplasm
(e.g. changing shape of cytoskeleton or regulating
enzymes) or function as a transcription factor
© 2011 Pearson Education, Inc.
Figure 11.15
Growth factor
Reception
Receptor
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
mRNA
Reception
Binding of epinephrine to G protein-coupled receptor (1 molecule)
Transduction
Inactive G protein
Cytoplasmic
response to a
signal:
the stimulation
of glycogen
breakdown by
epinephrine.
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
overall behavior of a cell, for example,
changes in cell shape
© 2011 Pearson Education, Inc.
RESULTS
What is this showing?
formin
Wild type yeast (with shmoos) Fus3
CONCLUSION
1 Mating
factor
activates
receptor.
Mating
factor G protein-coupled
Shmoo projection
forming
receptor
Formin
P
Fus3
GDP
GTP
2 G protein binds GTP
and becomes activated.
Fus3
Actin
subunit
P
Phosphorylation
cascade
Fus3
Formin
Formin
P
4 Fus3 phosphorylates
formin,
activating it.
P
3 Phosphorylation cascade
activates Fus3, which moves
to plasma membrane.
Microfilament
5 Formin initiates growth of
microfilaments that form
the shmoo projections.
Figure 11.17a
Wild type (with shmoos)
Fine-Tuning of the Response
• There are four aspects of fine-tuning to consider:
1. Amplification of the signal (and thus the
response)
2. Specificity of the response
3. Overall efficiency of response, enhanced by
scaffolding proteins
4. Termination of the signal
© 2011 Pearson Education, Inc.
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
© 2011 Pearson Education, Inc.
Figure 11.18
The specificity of cell signaling.
Signaling
molecule
Receptor
Relay
molecules
Response 1
Cell A. Pathway leads
to a single response.
Activation
or inhibition
Response 2
Response 3
Cell B. Pathway branches,
leading to two responses.
Response 4
Cell C. Cross-talk occurs
between two pathways.
Response 5
Cell D. Different receptor
leads to a different
response.
Figure 11.19
Signaling Efficiency: Scaffolding Proteins
and Signaling Complexes
Signaling
molecule
Plasma
membrane
Receptor
Three
different
protein
kinases
Scaffolding
protein
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
© 2011 Pearson Education, Inc.
Concept 11.5: Apoptosis integrates multiple
cell-signaling pathways
• Apoptosis is programmed or controlled cell
suicide
• WHY IS THIS FUNCTION CRITICAL?
© 2011 Pearson Education, Inc.
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
© 2011 Pearson Education, Inc.
Figure 11.20:
white blood cell apoptosis
2 m
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 studied in Caenorhabditis elegans
• In C. elegans, apoptosis results when proteins that
“accelerate” apoptosis override those that “put the
brakes” on apoptosis
© 2011 Pearson Education, Inc.
Figure 11.21
Ced-9
protein (active)
inhibits Ced-4
activity
Mitochondrion
Ced-9
(inactive)
Deathsignaling
molecule
Active Active
Ced-4 Ced-3
Receptor
for deathsignaling
molecule
Ced-4 Ced-3
Activation
cascade
Inactive proteins
(a) No death signal
Cell
forms
blebs
(b) Death signal
Other
proteases
Nucleases
Apoptotic Pathways and the Signals That
Trigger Them
• Caspases are the main proteases (what are
these?) 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
© 2011 Pearson Education, Inc.
• Apoptosis may be involved in some diseases (for
example, Parkinson’s and Alzheimer’s);
interference with apoptosis may contribute to
some cancers
© 2011 Pearson Education, Inc.
Figure 11.22:
apoptosis in paw development of the mouse
Interdigital tissue
Cells undergoing
apoptosis
Space between
1 mm
digits
REVIEW
1 Reception
2 Transduction
3 Response
Receptor
Activation
of cellular
response
Relay molecules
Signaling
molecule
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