Chapter 11 PowerPoint

Chapter 11
Cell Communication
Dr. Wendy Sera
Houston Community
College
Biology 1406
© 2014 Pearson Education, Inc.
Key Concepts in Chapter 11
1. External signals are converted to responses within the
cell.
2. Reception: A signaling molecule binds to a receptor
protein, causing it to change shape.
3. Transduction: Cascades of molecular interactions relay
signals from receptors to target molecules in the cell.
4. Response: Cell signaling leads to regulation of
transcription or cytoplasmic activities.
5. Apoptosis integrates multiple cell-signaling pathways.
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Cellular Messaging
 Cell-to-cell communication is essential for
multicellular organisms
 Cells can signal to each other and interpret the signals
they receive from other cells and the environment
 The same small set of cell signaling mechanisms
shows up in diverse species and processes
 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
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Figure 11.1—How does cell signaling trigger the desperate
flight of this impala?
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
 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
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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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α factor
Receptor
1 Exchange
of mating
factors
a
α
Yeast cell, a factor
Yeast cell,
mating type a
mating type α
2 Mating
a
α
3 New a/ cell
a/ α
Figure 11.2—
Communication
between mating
yeast cells
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Evolution of Cell Signaling, cont.
 Pathway similarities suggest that ancestral signaling
molecules that evolved in prokaryotes and singlecelled eukaryotes were adopted for use in their
multicellular descendants
 Example: The concentration of signaling molecules
allows the soil-dwelling myxobacteria (“slime
bacteria”) to share information about nutrient
availability.
 When food is scarce, starving cells secrete a molecule
that reaches neighboring cells and stimulates them to
aggregate and produce fruiting bodies that produces
spores that can survive harsh conditions.
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Figure 11.3—
Communication among
bacteria
1 Individual
rod-shaped
cells
2
2 Aggregation
in progress
0.5 mm
3 Spore-forming
structure
(fruiting body)
2.5 mm
Fruiting bodies
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Local and Long-Distance Signaling
 Cells in a multicellular organism communicate via
signaling molecules.
 Two types of signaling: 1) local signaling and 2)
long-distance signaling
 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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Plasma membranes
Gap junctions
between animal cells
Cell wall
Plasmodesmata
between plant cells
(a) Cell junctions
Figure 11.4—
Communication
by direct
contact
between cells
(b) Cell-cell recognition
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Local Signaling, cont.
 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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Local signaling
Electrical signal triggers
release of neurotransmitter.
Target cells
Neurotransmitter
diffuses across
synapse.
Secreting
cell
Secretory
vesicles
Target cell
Local regulator
(a) Paracrine signaling
(b) Synaptic signaling
Long-distance signaling
Endocrine cell
Target cell
specifically
binds
hormone.
Hormone
travels in
bloodstream.
Blood
vessel
Figure 11.5—Local
and long-distance
cell signaling by
secreted molecules
in animals
(c) Endocrine (hormonal) signaling
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Local Signaling, cont.
 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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Long-Distance Signaling
 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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Local signaling
Electrical signal triggers
release of neurotransmitter.
Target cells
Neurotransmitter
diffuses across
synapse.
Secreting
cell
Secretory
vesicles
Target cell
Local regulator
(b) Synaptic signaling
(a) Paracrine signaling
Long-distance signaling
Endocrine cell
Target cell
specifically
binds
hormone.
Figure 11.5—Local
and long-distance
cell signaling by
secreted molecules
in animals
Hormone
travels in
bloodstream.
Blood
vessel
(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 signals
went through three processes
 Reception
 Transduction
 Response
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Figure 11.6—Overview of cell signaling
EXTRACELLULAR
FLUID
1
CYTOPLASM
Plasma membrane
Reception
2
Transduction
3
Response
Receptor
1
2
Relay molecules
3
Activation
of cellular
response
Signaling
molecule
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The Three Stages of Cell Signaling, cont.
 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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Animation: Overview of Cell Signaling
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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 to
specific sites on receptor proteins that span the
plasma membrane
 There are three main types of membrane
receptors:
1. G protein-coupled receptors (largest family of
cell-surface receptors)
2. Receptor tyrosine kinases
3. Ion channel receptors
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Receptors: G Protein-coupled Receptors
 G protein-coupled receptors (GPCRs) are cell
surface transmembrane receptors that work with the
help of a G protein
 G proteins bind the energy-rich GTP
 G proteins are all very similar in structure
 GPCR systems are extremely widespread and diverse
in their functions
 60% of all medicines work by affecting G-protein
pathways!
 Bacterial infections: Cholera, Pertusis, Botulism
caused by toxins affecting G-protein function.
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Figure 11.8a—Exploring cell-surface transmembrane receptors
Signaling molecule binding site
Segment that
interacts with
G proteins
G protein-coupled receptor
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Figure 11.8—Exploring cell-surface transmembrane receptors
G protein-coupled
receptor
Plasma membrane
Inactive
enzyme
GTP
GDP
GDP
G protein
(inactive)
CYTOPLASM
Signaling
molecule
Activated
receptor
GTP
GDP
Enzyme
2
1
Activated
enzyme
GTP
GDP
Pi
Cellular
response
4
3
© 2014 Pearson Education, Inc.
Receptors: Receptor Tyrosine Kinases
 Receptor tyrosine kinases (RTKs) are
membrane 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
© 2014 Pearson Education, Inc.
Figure 11.8—Exploring cell-surface transmembrane receptors
Signaling molecule
(ligand)
 helix in the
Signaling molecule
Ligand-binding site
membrane
Tyrosines
CYTOPLASM
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
Dimer
2
1
Activated relay
proteins
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
P Tyr
6 ATP
Activated tyrosine
kinase regions
(unphosphorylated
dimer)
3
6 ADP
P Tyr
P Tyr
Tyr P
Tyr P
Tyr P
Fully activated
receptor tyrosine
kinase (phosphorylated dimer)
P Tyr
Tyr P
P Tyr
P Tyr
Tyr P
Tyr P
Cellular
response 1
Cellular
response 2
Inactive
relay proteins
4
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Receptors: Ligand-gated Ion Channel
 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
 Very important in nervous system function—
neurotransmitters are bind as ligands to ion
channels on the receiving neuron, causing the
channel to open.
© 2014 Pearson Education, Inc.
Figure 11.8—Exploring cell-surface transmembrane receptors
1
Signaling
molecule
(ligand)
Gate
closed
Ligand-gated
ion channel receptor
3
2
Ions
Gate open
Cellular
response
Plasma
membrane
Gate closed
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Intracellular Receptors
 Intracellular receptor proteins are found in the
cytoplasm 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
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Hormone
(aldosterone)
Figure 11.9—
Steroid hormone
interacting with an
intracellular
receptor
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
New
protein
NUCLEUS
CYTOPLASM
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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 greatly amplify a signal: A
few molecules 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 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
 In many pathways, the signal is transmitted by a
phosphorylation cascade
 Protein kinases transfer phosphates from ATP to
protein, a process called phosphorylation
 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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Signaling molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
Figure 11.10—A
phosphorylation
cascade
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
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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 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—Cyclic AMP
Adenylyl cyclase
Pyrophosphate
ATP
cAMP
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Cyclic AMP, cont.
 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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First messenger
(signaling molecule
such as epinephrine)
Adenylyl
cyclase
G protein
GTP
G protein-coupled
receptor
ATP
cAMP
Second
messenger
Protein
kinase A
Figure 11.12—cAMP as a
second messenger in a G
protein signaling pathway
Cellular responses
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Calcium Ions
 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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Endoplasmic
reticulum (ER)
Plasma
membrane
ATP
Mitochondrion
Nucleus
Ca2+
pump
ATP
CYTOSOL ATP
EXTRACELLULAR
FLUID
Key
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High [Ca2+]
Low [Ca2+]
Figure 11.13—The
maintenance of
calcium ion
concentrations in an
animal cell
14
Calcium Ions, cont.
 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—Calcium and IP3 in signaling pathways
Signaling molecule
(first messenger)
G protein
EXTRACELLULAR
FLUID
GTP
CYTOSOL
G protein-coupled
receptor
Endoplasmic
reticulum (ER)
lumen
DAG
Phospholipase C
IP3-gated
calcium channel
Ca2+
Nucleus
Ca2+
(second
messenger)
PIP2
IP3
(second messenger)
Various
proteins
activated
Cellular
responses
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Animation: Signal Transduction Pathways
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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”
 Ultimately, a signal transduction pathway leads to
regulation of one or more cellular activities
 The response may occur in the cytoplasm
(cytoplasmic responses) or in the nucleus
(nuclear responses)
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Nuclear Response
 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—
Nuclear
responses to
a signal: the
activation of a
specific gene
by a growth
factor
Growth factor
Reception
Receptor
Phosphorylation
cascade Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
mRNA
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Cytoplasmic Responses
 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
 Signaling pathways can also affect the overall
behavior of a cell, for example, a signal could lead
to cell division
© 2014 Pearson Education, Inc.
Figure 11.16—Cytoplasmic response to a signal: the stimulation of
glycogen breakdown by epinephrine (adrenaline)
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 (10 4)
Inactive
phosphorylase kinase
Response
Active phosphorylase kinase (105)
Glycogen
Inactive
glycogen phosphorylase
Glucose 1-phosphate
(108 molecules)
Active glycogen phosphorylase (106)
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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
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Concept 11.5: Apoptosis integrates multiple
cell-signaling pathways
 Cells that are infected or damaged or have
reached the end of their functional lives often
undergo “programmed cell death”
 Apoptosis is the best understood type
 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 11.19—Apoptosis of a human white blood cell
2 µm
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Apoptotic Pathways and the Signals That
Trigger Them
 In humans and other mammals, several different
pathways, including about 15 caspases, can carry out
apoptosis
 Caspases are the main proteases—enzymes that cut
up proteins
 Apoptosis can be triggered by signals from outside the
cell or inside it, such as:
1. An extracellular death-signaling ligand
2. Irreparable DNA damage in the nucleus
3. Excessive protein misfolding in the ER
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Apoptotic Pathways, cont.
 Apoptosis evolved early in animal evolution and is
essential for the development and maintenance of
all animals
 For example, apoptosis is a normal part of
embryonic development of hands and feet in
humans (and paws in other mammals)
 Apoptosis may be involved in some diseases
(for example, Parkinson’s and Alzheimer’s);
interference with apoptosis may contribute to
some cancers
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Figure 11.21—Effect of apoptosis during paw development
in the mouse
Interdigital
tissue
Cells
undergoing
apoptosis
1 mm
Space
between
digits
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