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Cell Communication
Cell Communication
• Cell-to-cell communication is absolutely
essential for multicellular organisms and
is also important for many unicellular
organisms
• Cells must communicate to coordinate
their activities
The “Cellular Internet”
Biologists have discovered some universal
mechanisms of cellular regulation,
involving the same small set of cellsignaling mechanisms
• External
signals are
converted into
responses
within the cell
Evolution of Cell Signaling
Yeast cells
• Identify their mates by cell signaling
1 Exchange of
mating factors.
Each cell type
secretes a
mating factor
that binds to
receptors on
the other cell
type.
 factor
Receptor

a
Yeast cell,
mating type a
 factor
Yeast cell,
mating type 
2 Mating. Binding
of the factors to
receptors
induces changes
in the cells that
lead to their
fusion.

a
3 New a/ cell.
The nucleus of
the fused cell
includes all the
genes from the
a and  cells.
a/
Methods used by Cells to
Communicate
Cell-Cell communication
Cell Signaling using chemical messengers
Plasma
membranes
Local signaling
Target cell
Secretory
vesicle
Gap junctions
between
animal cells
Plasmodesmata
between plant
cells
Local regulator
diffuses through
extracellular fluid
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across
synapse
Target cell
is stimulated
1. Local signaling over short distances
• Cell-Cell Recognition
• Local regulators
Paracrine (growth factors)
Synaptic (neurotransmitters)
2. Long distance signaling
• Hormones
Cell-Cell Communication
Animal and plant cells
• Have cell junctions that directly connect
the cytoplasm of adjacent cells
Plasma membranes
Gap junctions
between animal cells
Figure 11.3
Plasmodesmata
between plant cells
(a) Cell junctions. Both animals and plants have cell junctions that allow molecules
to pass readily between adjacent cells without crossing plasma membranes.
Cell-Cell Communication
Animal cells use gap junctions to send signals
• cells must be in direct contact
• protein channels connecting two adjoining
cells
Gap junctions
between animal cells
Cell-Cell Communication
Plant cells use plasmodesmata to send signals
• cells must be in direct contact
• gaps in the cell wall connecting the two adjoining
cells together
Plasmodesmata between
plant cells
Local Signaling: Cell-Cell Recognition
In local signaling, animal cells may communicate
via direct contact
• Membrane bound cell surface molecules
• Glycoproteins
• Glyolipids
(Cell-cell recognition. Two cells in an animal may communicate
by interaction between molecules protruding from their
surfaces.
Local Signaling: Local Regulators
In other cases, animal cells
• Communicate using local regulators
• Only work over a short distance
Local signaling
Target cell
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across
synapse
Secretory
vesicle
Local regulator
diffuses through
extracellular fluid
(a) Paracrine signaling. A secreting cell acts
on nearby target cells by discharging
molecules of a local regulator (a growth
factor, for example) into the extracellular
fluid.
Target cell
is stimulated
(b) Synaptic signaling. A nerve cell
releases neurotransmitter molecules
into a synapse, stimulating the
target cell.
Long-distance Signaling: Hormones
In long-distance signaling
• Both plants and animals use hormones
Long-distance signaling
Endocrine cell
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
(c) Hormonal signaling. Specialized
endocrine cells secrete hormones
into body fluids, often the blood.
Hormones may reach virtually all
body cells.
Long-Distance Signaling
Nervous System in Animals
 Electrical signals through neurons
Endocrine System in Animals
 Uses hormones to transmit messages
over long distances
Plants also use hormones
 Some transported through vascular
system
 Others are released into the air
How do Cells Communicate?
Earl W. Sutherland
• Discovered how the hormone epinephrine
acts on cells
How do Cells Communicate?
Sutherland suggested that cells receiving
signals went through three processes
Reception
Transduction
Response
Called Signal transduction pathways
• Convert signals on a cell’s surface into
cellular responses
• Are similar in microbes and mammals,
suggesting an early origin
How do Cells Communicate?
The process must involve three stages
1. Reception - a chemical signal binds to
a cellular protein, typically at the cell’s
surface
2. Transduction - binding leads to a change
in the receptor that triggers a series of
changes along a signal-transduction
pathway
3. Response - the transduced signal
triggers a specific cellular response
Signal Transduction Animation
• http://media.pearsoncmg.com/bc/bc_cam
pbell_biology_7/media/interactivemedia/a
ctivities/load.html?11&A
• http://www.wiley.com/legacy/college/boye
r/0470003790/animations/signal_transduct
ion/signal_transduction.htm
Signal molecules and Receptor
Proteins
A cell targeted by a particular chemical signal
has a receptor protein that recognizes the
signal molecule
• recognition occurs when the signal binds
to a specific site on the receptor because it
is complementary in shape
When ligands (small molecules that bind
specifically to a larger molecule) attach to
the receptor protein, the receptor typically
undergoes a change in shape
• this may activate the receptor so that it can
interact with other molecules
Signal Molecules
• most signal molecules are water-soluble
and too large to pass through the
plasma membrane
• they influence cell activities by binding
to receptor proteins on the plasma
membrane
– binding leads to change in the shape
of the receptor
– these trigger changes in the
intracellular environment
There are three common types of
membrane receptor proteins:
• G-protein coupled receptors
• Receptor tyrosine-kinases
• Ion channel receptors
1. Reception
A signal molecule, a ligand, binds to a receptor
protein in a lock and key fashion, causing the
receptor to change shape.
• Most receptor
proteins are in the
cell membrane but
some are inside
the cell.
G Protein- Coupled Receptor
• the receptor consists of seven alpha
helices spanning the membrane
G-Protein Receptors
Plasma
membrane
G protein-coupled
receptor
Activated
receptor
Inactive
enzyme
Signaling molecule
Enzyme
GDP
2
1
CYTOPLASM
G protein
(inactive)
GDP
GTP
Activated
enzyme
i
GTP
GDP
P
4
3
Cellular response
• effective signal molecules include yeast
mating factors, epinephrine, other
hormones, and neurotransmitters
Several human diseases are the results of
activities, including bacterial infections, that
interfere with G protein function
botulism
cholera
pertussis
Receptor tyrosine kinases
Signal-binding site
Signal
molecule
Signal
molecule
Helix in the
Membrane
Tyr
Tyrosines
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
Tyr P
Tyr P
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
P Tyr
P Tyr
P Tyr
Tyr P
Tyr P
Tyr P
Inactive
relay proteins
Cellular
response 1
Cellular
response 2
Ligand-gated Ion Channels
• Ligand-gated ion channels
are protein pores that open
or close in response to a
chemical signal
• this allows or blocks ion
flow, such as Na+ or Ca2+
• binding by a ligand to the
extracellular side changes
the protein’s shape and
opens the channel
• ion flow changes the
concentration inside the
cell
Ion Channel Receptors
Gate
closed
1
• Very important in the
nervous system
• Signal triggers the
opening of an ion
channel
– Depolarization
– Triggered by
neurotransmitters
Ions
Signaling
molecule
(ligand)
Ligand-gated
ion channel receptor
Plasma
membrane
2
Gate open
Cellular
response
3
Gate closed
2. Transduction
• Transduction: Cascades of molecular
interactions relay signals from receptors
to target molecules in the cell
• Multistep pathways
– Can amplify a signal (Amplifies the signal by
activating multiple copies of the next component in
the pathway)
– Provide more opportunities for coordination
and regulation
• At each step in a pathway, the signal is
transduced into a different form,
commonly a conformational change in a
protein.
Signaling molecule
Receptor
Transduction:
Activated relay
molecule
A Phosphorylation Cascade
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
Protein Phosphorylation and
Dephosphorylation
Many signal pathways
• Include phosphorylation cascades
• In this process, a series of protein kinases
add a phosphate to the next one in line,
activating it
• Phosphatase enzymes then remove the
phosphates
A phosphorylation cascade
Signal molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
A1relay molecule
activates protein kinase 1.
2 Active protein kinase 1
transfers a phosphate from ATP
to an inactive molecule of
protein kinase 2, thus activating
this second kinase.
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
Pi
PP
Inactive
protein kinase
3
5 Enzymes called protein
phosphatases (PP)
catalyze the removal of
the phosphate groups
from the proteins,
making them inactive
and available for reuse.
P
Active
protein
kinase
2
ADP
3 Active protein kinase 2
then catalyzes the phosphorylation (and activation) of
protein kinase 3.
ATP
ADP
Pi
Active
protein
kinase
3
PP
Inactive
protein
P
4 Finally, active protein
kinase 3 phosphorylates a
protein (pink) that brings
about the cell’s response to
the signal.
ATP
ADP
P
PP
i
P
Active
protein
Cellular
response
The transduction stage of signaling is often a
multistep process that amplifies the signal.
• About 1%
of our
genes are
thought to
code for
kinases.
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ctivities/load.html?11&C
Small Molecules and Ions as Second
Messengers
Secondary messengers
• Are small, nonprotein, water-soluble
molecules or ions
Cyclic AMP
• Many G-proteins trigger the formation of cAMP,
which then acts as a second messenger in
cellular pathways.
First messenger
(signal molecule
such as epinephrine)
G protein
G-protein-linked
receptor
Adenylyl
cyclase
GTP
ATP
cAMP
Protein
kinase A
Cellular responses
Cyclic AMP
Cyclic AMP (cAMP)
• Is made from ATP
NH2
N
N
O
O
O
N
N
–
O P O P O P O Ch2
O
O
O
N
N
O
Pyrophosphate
P Pi
O
O
CH2
Phoshodiesterase
HO P O CH2
O
H2O
O
OH OH
OH
Cyclic AMP
N
N
O
O
O
P
N
N
N
N
Adenylyl cyclase
O
OH OH
ATP
NH2
NH2
AMP
3. Response
Growth factor
Receptor
• Many possible
outcomes
• This example
shows a
transcription
response
Phosphorylation
cascade
Reception
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
DNA
Gene
NUCLEUS
mRNA
Response
• Specificity of the
signal
Signaling
molecule
– The same
signal molecule
can trigger
different
responses
– Many
responses can
come from one
signal!
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.
• The signal
can also
trigger an
activator or
inhibitor
• The signal
can also
trigger
multiple
receptors
and different
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.
Response- cell signaling leads to regulation
of transcription (turn genes on or off) or
cytoplasmic activities.
Long-distance Signaling - Intracellular signaling
includes hormones that are hydrophobic and can
cross the cell membrane.
Once inside the cell, the
hormone attaches to a
protein that takes it into
the nucleus where
transcription can be
stimulated.
Testosterone acts as a
transcription factor.
• Steroid hormones
– Bind to intracellular receptors
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
1 The steroid
hormone testosterone
passes through the
plasma membrane.
2 Testosterone binds
to a receptor protein
in the cytoplasm,
activating it.
3 The hormonereceptor complex
enters the nucleus
and binds to specific
genes.
4 The bound protein
stimulates the
transcription of
the gene into mRNA.
5 The mRNA is
translated into a
specific protein.
Signaling Efficiency: Scaffolding
Proteins and Signaling
Complexes
• Scaffolding proteins
– Can increase the signal transduction
efficiency
Signal
molecule
Plasma
membrane
Recepto
r
Scaffolding
protein
Three
different
protein
kinases
Termination of the Signal
• Signal response is terminated quickly
– By the reversal of ligand binding