Chapter 11
Cell Communication
PowerPoint Lectures for
Biology, Seventh Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Overview: The Cellular Internet
• Cell-to-cell communication is essential for
multicellular organisms
• Biologists have discovered some universal
mechanisms of cellular regulation
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Concept 11.1: External signals are converted into
responses within the cell
• Microbes are a window on the role of cell signaling
in the evolution of life
Copyright © 2005 Pearson Education, Inc. publishing as 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
• Signal transduction pathways convert signals on
a cell’s surface into cellular responses
• Pathway similarities suggest that ancestral
signaling molecules evolved in prokaryotes and
have since been adopted by eukaryotes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-2
Exchange of
mating factors
a factor
Receptor
a
a
Yeast cell, a factor
mating type a
Yeast cell,
mating type a
Mating
a
a
New a/a cell
a/a
Local and Long-Distance Signaling
• Cells in a multicellular organisms 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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-3
Plasma membranes
Gap junctions
between animal cells
Cell junctions
Cell-cell recognition
Plasmodesmata
between plant cells
• In many other cases, animal cells communicate
using local regulators, messenger molecules that
travel only short distances
• In long-distance signaling, plants and animals use
chemicals called hormones
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-4
Local signaling
Long-distance signaling
Target cell
Secreting
cell
Local regulator
diffuses through
extracellular fluid
Paracrine signaling
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Endocrine cell
Neurotransmitter
diffuses across
synapse
Secretory
vesicle
Target cell
is stimulated
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
Synaptic signaling
Hormonal signaling
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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-5_1
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane
Reception
Receptor
Signal
molecule
Transduction
LE 11-5_2
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane
Reception
Transduction
Receptor
Relay molecules in a signal transduction
pathway
Signal
molecule
LE 11-5_3
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane
Reception
Transduction
Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction
pathway
Signal
molecule
Concept 11.2: Reception: A signal molecule binds
to a receptor protein, causing it to change shape
• The binding between a signal molecule (ligand)
and receptor is highly specific
• A conformational change in a receptor is often the
initial transduction of the signal
• Most signal receptors are plasma membrane
proteins
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-6
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
The steroid
hormone testosterone
passes through the
plasma membrane.
Testosterone binds
to a receptor protein
in the cytoplasm,
activating it.
The hormonereceptor complex
enters the nucleus
and binds to specific
genes.
DNA
The bound protein
stimulates the
transcription of
the gene into mRNA.
mRNA
NUCLEUS
New protein
The mRNA is
translated into a
specific protein.
CYTOPLASM
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-linked receptors
– Receptor tyrosine kinases
– Ion channel receptors
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• A G-protein-linked 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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-7aa
Signal-binding site
Segment that
interacts with
G proteins
G-protein-linked receptor
• Receptor tyrosine kinases are membrane
receptors that attach phosphates to tyrosines
• A receptor tyrosine kinase can trigger multiple
signal transduction pathways at once
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-7b
Signal
molecule
Signal-binding site
a Helix in the
membrane
Signal
molecule
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
CYTOPLASM
Dimer
Activated relay
proteins
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
6
ATP
Activated tyrosinekinase regions
(unphosphorylated
dimer)
6 ADP
P Tyr
P Tyr
P Tyr
Tyr
P
P
Tyr P
Tyr
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
P Tyr
P Tyr
P Tyr
P
Tyr P
Tyr P
Tyr
Inactive
relay proteins
Cellular
response 1
Cellular
response 2
• An 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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-7c
Signal
molecule
(ligand)
Gate
closed
Ligand-gated
ion channel receptor
Ions
Plasma
membrane
Gate open
Cellular
response
Gate closed
Concept 11.3: Transduction: Cascades of molecular interactions
relay signals from receptors to target molecules in the cell
• 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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
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 conformational change
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Protein Phosphorylation and Dephosphorylation
• In many pathways, the signal is transmitted by a
cascade of protein phosphorylations
• Phosphatase enzymes remove the phosphates
• This phosphorylation and dephosphorylation
system acts as a molecular switch, turning
activities on and off
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-8
Signal 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
ATP
ADP
Pi
Active
protein
kinase
3
PP
Inactive
protein
P
ATP
P
ADP
Pi
PP
Active
protein
Cellular
response
Small Molecules and Ions as Second Messengers
• Second messengers are small, nonprotein, watersoluble molecules or ions
• The extracellular signal molecule that binds to the
membrane is a pathway’s “first messenger”
• Second messengers can readily spread
throughout cells by diffusion
• Second messengers participate in pathways
initiated by G-protein-linked receptors and
receptor tyrosine kinases
Copyright © 2005 Pearson Education, Inc. publishing as 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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-9
Phosphodiesterase
Adenylyl cyclase
Pyrophosphate
P
ATP
H2O
Pi
Cyclic AMP
AMP
• Many signal molecules trigger formation of cAMP
• Other components of cAMP pathways are G
proteins, G-protein-linked 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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-10
First messenger
(signal molecule
such as epinephrine)
Adenylyl
cyclase
G protein
G-protein-linked
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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-11
EXTRACELLULAR
FLUID
Plasma
membrane
Ca2+
pump
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
Endoplasmic
reticulum (ER)
ATP
Key
Ca2+
pump
High [Ca2+]
Low [Ca2+]
• 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 second messengers
Animation: Signal Transduction Pathways
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-12_1
EXTRACELLULAR Signal molecule
FLUID
(first messenger)
G protein
DAG
GTP
G-protein-linked
receptor
IP3-gated
calcium channel
Endoplasmic
Ca2+
reticulum (ER)
CYTOSOL
Phospholipase C
PIP2
IP3 (second
messenger)
LE 11-12_2
EXTRACELLULAR Signal molecule
FLUID
(first messenger)
G protein
DAG
GTP
G-protein-linked
receptor
Phospholipase C
IP3 (second
messenger)
IP3-gated
calcium channel
Endoplasmic
Ca2+
reticulum (ER)
CYTOSOL
PIP2
Ca2+
(second
messenger)
LE 11-12_3
EXTRACELLULAR Signal molecule
FLUID
(first messenger)
G protein
DAG
GTP
G-protein-linked
receptor
Phospholipase C
PIP2
IP3 (second
messenger)
IP3-gated
calcium channel
Endoplasmic
Ca2+
reticulum (ER)
CYTOSOL
Ca2+
(second
messenger)
Various
proteins
activated
Cellular
responses
Concept 11.4: Response: Cell signaling leads to
regulation of cytoplasmic activities or transcription
• The cell’s response to an extracellular signal is
sometimes called the “output response”
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cytoplasmic and Nuclear 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 pathways regulate the activity of enzymes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-13
Reception
Binding of epinephrine to G-protein-linked 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)
• Many other 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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-14
Growth factor
Reception
Receptor
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription Active
transcription
factor
factor
P
Response
DNA
Gene
NUCLEUS
mRNA
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
Copyright © 2005 Pearson Education, Inc. publishing as 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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The Specificity of Cell Signaling
• Different kinds of cells have different collections of
proteins
• These differences in proteins give each kind of cell
specificity in detecting and responding to signals
• The response of a cell to a signal depends on the
cell’s particular collection of proteins
• Pathway branching and “cross-talk” further help
the cell coordinate incoming signals
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-15
Signal
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
• Scaffolding proteins can increase the signal
transduction efficiency
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 11-16
Signal
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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings