Transcript Topic 9: Cell Communication

Chapter 11
Cell Communication
Cell Communication
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
Cells Recognize and Respond
to External Signals
Microbes provide a glimpse of the role of cell signaling in the evolution of
life
Evolution of
Cell Signaling
 The yeast, Saccharomyces
cerevisiae, has two mating
types, a and 
 different mating types
locate each other via
secreted factors
 factor
Receptor
1 Exchange
of mating
factors

a
a factor
Yeast cell,
Yeast cell,
mating type a
mating type 
2 Mating

a
 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
3 New a/ cell
a/
Communication
in Bacteria:
Cell Signaling
1 Individual
rod-shaped
cells
2 Aggregation
in progress
0.5 mm
3 Spore-forming
structure
(fruiting body)
Quorum sensing
to signal other
cells to gather!
2.5 mm
Fruiting bodies
Signaling in Multiceullar Organisms:
“Local Signaling”
 Multicellular organism’s cells 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
Figure 11.4
Plasma membranes
Gap junctions
between animal cells
(a) Cell junctions
(b) Cell-cell recognition
Plasmodesmata
between plant cells
 In many other cases, animal cells communicate using local
regulators, messenger molecules that travel only short distances
 The ability of a cell to respond to a signal depends on whether or not it
has a receptor specific to that signal
Local Signaling
Local Regulators: work over very short distances
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
Long-distance signaling
Endocrine cell
Blood
vessel
• Hormones are used in longdistance signaling.
• Both plants and animals
have hormones!
• AKA endocrine signaling
Hormone travels
in bloodstream.
Target cell
specifically
binds
hormone.
(c) Endocrine (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
Right-click slide / select “Play”
© 2011 Pearson Education, Inc.
Reception: A cell recognizes the signal!
What determines if a cell will respond to a signal?
EXTRACELLULAR
FLUID
1 Reception
Receptor
Signaling
molecule
CYTOPLASM
Plasma membrane
Transduction: Converting the
Signal to Action
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
Receptor
Relay molecules in a signal transduction
pathway
Signaling
molecule
Response: Specific Cellular Action
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
Reception: Signaling molecule and
Receptor Proteins
The binding between a signal molecule (ligand) and receptor is highly
specific
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
 G protein-coupled receptors
 Receptor tyrosine kinases
 Ion channel receptors
Type 1: G-protein Coupled Receptors
 G protein-coupled receptors
(GPCRs) are the largest family of cellsurface receptors
Signaling molecule binding site
 Work 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
Segment that
interacts with
G proteins
G protein-coupled receptor
G-protein Function: “On” and “Off”
G protein-coupled
receptor
Plasma
membrane
Activated
receptor
1
Inactive
enzyme
GTP
GDP
GDP
CYTOPLASM
Signaling
molecule
Enzyme
G protein
(inactive)
2
GTP
GDP
Activated
enzyme
GTP
GDP
Pi
3
Cellular response
4
Energy source GTP turns on the G protein
GDP turns it off
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
 Active form is a dimer
 Abnormal functioning of
RTKs is associated with
many types of cancers
RTK – Activation Through Dimerization
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
Ligand-Gated Ion Channels
 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
Ligand-Gated Ion Channel Activation
1
Signaling
molecule
(ligand)
3
2
Gate
closed
Ions
Plasma
Ligand-gated
membrane
ion channel receptor
Gate closed
Gate
open
Cellular
response
Signaling molecule binds to allow specific ions into cell
These ions produce cellular responses (Ca+2 one of the most important!)
Intracellular Receptors: Hormones
 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
 steroid and thyroid hormones
of animals
 Can act as a transcription
factor, turning on specific
genes
Hormone Activation
 The signaling molecule is
permeable to the membrane
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
 The receptor is found inside the
cell
DNA
NUCLEUS
CYTOPLASM
Figure 11.9-2
Hormone Activation
 Hormone and receptor bond,
activating the complex
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
NUCLEUS
CYTOPLASM
Figure 11.9-3
Hormone Activation
 One possible function of these
complexes are to initiate the
synthesis of specific genes
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
 Here the complex enters the
nucleus , acting as a transcription
factor
DNA
NUCLEUS
CYTOPLASM
Figure 11.9-4
Hormone Activation
 The target RNA is made and
exported for protein production
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
Figure 11.9-5
Hormone Activation
 Target protein is synthesized,
completing the initial signal’s
response
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
Transduction: Signal Transduction
Cascades relay signals from receptors to
target molecules in the cell
Multistep pathways can amplify a signal and provide more opportunities
for coordination and regulation of the cellular response
Signal Transduction Pathways
 Proteins in the cytosol relay a signal
from receptor
 Like 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
 One of the most common methods of
regulating the signal is through
phosphorylation and
dephosphorylation
Protein Phosphorylation and
Dephosphorylation: Molecular Switches
 Protein kinases transfer phosphates from ATP to protein phosphorylation
 Protein phosphatases remove the phosphates  dephosphorylation
 This phosphorylation and dephosphorylation system acts as a molecular
switch, turning activities on and off or up or down, as required
Signaling molecule
Receptor
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
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
Active
protein
kinase
3
PP
Pi
Inactive
protein
P
ATP
P
ADP
PP
Pi
Active
protein
Secondary Messengers:
Small Molecules and Ions
 The extracellular signal molecule (ligand) 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
Cyclic AMP: Activation
• ATP is made into cAMP in response to an extracellular signal
Adenylyl cyclase
Pyrophosphate
P
ATP
Pi
cAMP
Cyclic AMP: Regulation
Phosphodiesterase
H2O
cAMP
H2O
AMP
cAMP
Pathway
 Many signal
molecules trigger
formation of cAMP
 cAMP usually
activates protein
kinase A, which
phosphorylates
various other
proteins
 Regulation of cell
metabolism is
provided by Gprotein systems that
inhibit adenylyl
cyclase
First messenger
(signaling molecule
such as epinephrine)
G protein
G protein-coupled
receptor
Adenylyl
cyclase
GTP
ATP
Second
cAMP messenger
Protein
kinase A
Cellular responses
EXTRACELLULAR
FLUID
Plasma
membrane
Ca2
pump
Mitochondrion
ATP
Calcium
Ions
 Calcium ions (Ca2+) act
as a second
messenger in many
pathways
Nucleus
 Cells can regulate its
concentration
CYTOSOL
Ca2
pump
ATP
Key
High [Ca2 ]
Ca2
pump
Endoplasmic
reticulum
(ER)
Low [Ca2 ]
 A signal relayed by a
signal transduction
pathway may trigger an
increase in calcium in
the cytosol
Calcium and Inositol Triphosphate
 Pathways leading to the release of calcium involve inositol triphosphate
(IP3) and diacylglycerol (DAG) as additional second messengers
Animation: Signal Transduction Pathways
Right-click slide / select “Play”
© 2011 Pearson Education, Inc.
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
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)
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
Response: Cell signaling leads to
regulation of transcription or
cytoplasmic activities
•The cell’s response to an extracellular signal is sometimes called the
“output response”
Nuclear and
Cytoplasmic
Responses
Growth factor
Reception
Receptor
 Signal transduction pathways
lead to regulation of cellular
activities
Phosphorylation
cascade
Transduction
 The response can be
cytoplasm or in the nucleus
CYTOPLASM
 Regulate synthesis of proteins,
usually by turning genes on or
off
 Molecules may function as a
transcription factor
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
mRNA
Signals Can
Regulate
Overall Cell
Behavior
formin
Fus3
Wild type (with shmoos)
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.
Fine-Tuning of the Response
 There are four aspects of fine-tuning 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
Fine Tuning 1
Responses:
Amplification
of Signal
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)
 Enzyme cascades amplify the
cell’s response
ATP
Cyclic AMP (104)
 At each step, the number of
activated products is much
greater than in the preceding
step
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)
Fine Tuning 2: The Specificity of Cell
Signaling and Coordination of the Response
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.
Signaling
 Different kinds of molecule
cells have
different
collections of
proteins
 Respond to
different signals
 Same signal can
have different
effects in cells
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.
Pathway
branching and
“cross-talk”
further help the
cell coordinate
incoming
signals
Activation
or inhibition
Response 4
Cell C. Cross-talk occurs
between two pathways.
Response 5
Cell D. Different receptor
leads to a different
response.
Fine Tuning 3:Signaling Efficiency:
Scaffolding Proteins and Signaling
Complexes
 Scaffolding proteins are large relay proteins to which other relay proteins
are attached and can increase the signal transduction efficiency by grouping
together different proteins involved in the same pathway
Signaling
molecule
Plasma
membrane
Receptor
Scaffolding
protein
Three
different
protein
kinases
Fine Tuning 4: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
Signal Review
1 Reception
2 Transduction
3 Response
Receptor
Activation
of cellular
response
Relay molecules
Signaling
molecule