Transcript Cell Communication

CELL COMMUNICATION
SIGNAL TRANSDUCTION PATHWAYS
LOCAL 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-4
Plasma
membranes
Gap junctions
between animal cells
(a) Cell junctions
(b) Cell-cell
recognition
Plasmodesmata
between plant cells
Fig. 11-5ab
Local signaling
Target cell
Secretin
g
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
Target cell
is stimulated
(b) Synaptic
signaling
LONG-DISTANCE SIGNALING
• In long-distance signaling, animals and plants use
chemical messengers called hormones.
• Hormones are chemicals made in one area of the
body that are delivered to other areas.
Fig. 11-5c
Long-distance signaling
Endocrine
cell
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
(c) Hormonal
signaling
WHAT ARE SIGNAL TRANSDUCTION
PATHWAYS?
• 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.
• In general there are 3 steps:
• 1) Reception
• 2) Transduction
• 3) Response
Fig. 11-6-1
EXTRACELLULAR
FLUID
1 Reception
Recepto
r
Signaling
molecule
CYTOPLASM
Plasma
membrane
Fig. 11-6-2
CYTOPLASM
EXTRACELLULAR
FLUID
Plasma membrane
1 Reception
2 Transduction
Receptor
Relay molecules in a signal transduction pathway
Signaling
molecule
Fig. 11-6-3
CYTOPLASM
EXTRACELLULAR
FLUID
Plasma membrane
1 Reception
2 Transduction
3 Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway
Signaling
molecule
STEP 1: RECEPTION
• In Step 1, Reception: a signaling molecule binds to a
receptor protein, causing it to change shape.
• Ligand: the signaling molecule
• Receptor: a molecule (usually a protein) on the
surface of a cell that recognizes and binds to a
ligand
• The binding between a ligand and its’ receptor is
highly specific.
RECEPTORS IN THE PLASMA
MEMBRANE
• Most water-soluble signal molecules bind to specific
sites on receptor proteins in the plasma membrane
• Examples of membrane receptors:
• G protein-coupled receptors
• Ion channel receptors
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
G-Protein-Coupled Receptors
• A G protein-coupled 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 © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-7b
Plasma
membrane
G proteincoupled
receptor
Activated
receptor
Signaling molecule
GDP
CYTOPLASM
GDP
Enzyme
G protein
(inactive)
GTP
2
1
Activated
enzyme
GTP
GDP
Pi
Cellular response
3
4
Inactive
enzyme
Ligand-gated Ion Channel
Receptor
• 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-7d
1 Signaling
molecule
(ligand)
Gate
closed
Plasma
membran
e
Ligand-gated
ion channel
receptor
2
Ions
Gate
open
Cellular
response
3
Gate
closed
STEP 2: TRANSDUCTION
• In Step 2, Transduction: Cascades of molecular
interactions relay signals from receptors to target
molecules in the cell
• Transduction: the conversion of a signal outside the
cell to a form that can bring about a specific
cellular response.
SIGNAL TRANSDUCTION PATHWAYS
• Signal transduction usually involves multiple steps,
called a signal cascade.
• Multi-step pathways (signaling cascades) can
amplify a signal; even just a few molecules can
cause a large cell response.
• Advantage: multi-step pathways can provide for
more ways to coordinate and regulate the
response.
• Multi-step pathways also allow for more specificity
in the response.
Fig. 11-9
Signaling
molecule
Receptor
Activated
relay
molecule
Inactive
protein kinase
1
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
Pi
ADP
P
Active
protein
kinase
2
PP
Inactive
protein kinase
3
Pi
ATP
ADP
Active
protein
kinase
3
PP
Inactive
protein
ATP
Pi
PP
ADP
P
P
Active
protein
Cellular
response
SECOND MESSENGERS
• The extracellular signal molecule that binds to the
receptor is a pathway’s “first messenger”
• Second messengers are small, non-protein, watersoluble molecules or ions that spread throughout a
cell by diffusion
• Second messengers participate in pathways initiated
by G protein-coupled receptors
• Cyclic AMP and calcium ions are common second
messengers
Copyright © 2008 Pearson Education, Inc., publishing as Pearson 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 © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-10
Conversion of ATP to cAMP to AMP
Adenylyl
cyclase
Phosphodiesterase
Pyrophosphate
P
ATP
Pi
cAMP
AMP
Triggering the making of cAMP
• Many signal molecules trigger formation of cAMP
• cAMP usually activates protein kinase A, which
phosphorylates various other proteins
• Further regulation of cell metabolism is provided by Gprotein systems that inhibit adenylyl cyclase.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-11
First messenger
Adenyly
l
cyclase
G protein
G proteincoupled
receptor
GTP
ATP
cAM
P
Second
messenger
Protein
kinase A
Cellular responses
CALCIUM IONS
• Calcium ions (Ca2+) act as a second messenger in
many pathways
• Calcium is an important second messenger because
cells can regulate its concentration
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-12
EXTRACELLULAR
FLUID
Plasma
membran
e
Ca2+ pump
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
Endoplasmic
reticulum (ER)
ATP
Key
High [Ca2+]
Low [Ca2+]
Ca2+
pump
STEP 3: RESPONSE
• In Step 3, Response: Cell signaling leads to
regulation of transcription or a change in the cell’s
activities. This is sometimes called the “output
response”.
• Transcription: One of the processes involved in
genes that determines which proteins will be made
in the cell
• Other cell signaling pathways may regulate the
action of an enzyme.
Fig. 11-14
Growth factor
Receptor
Receptio
n
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
Response
P
DNA
Gen
e
NUCLEUS
mRNA
Fig. 11-15
Reception
Binding of epinephrine to G protein-coupled receptor (1 molecule)
Transduction
The
stimulation of
glycogen
breakdown
by
epinephrine:
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
Glycoge
n
Glucose-1-phosphate
(108 molecules)
This is an
example of a
phosphorylation
cascade
CHANGES IN SIGNAL TRANSDUCTION
PATHWAYS
• Changes in signal transduction pathways can alter
cellular response.
• For Example: Conditions where signal transduction is
blocked or defective can be deleterious (bad),
preventative, or prophylactic (good).
Fig. 11-UN1
What would happen if one of the relay
molecules was defective?
1
Reception
2
Transduction
3 Response
Receptor
Relay
molecules
Signaling
molecul
e
Activation
of cellular
response
QUESTION: HOW DOES CAFFEINE
WORK ON THE BRAIN?
• Caffeine has many effects on the body, but the
most noticeable is that it keeps us awake.
• The caffeine molecule is large and polar, so it
doesn’t diffuse easily across the cell membrane.
• Instead it binds to receptors on the surfaces of
nerve cells in the brain.
ADENOSINE
• Adenosine (a nucleoside) accumulates in the brain
when a person is under stress or has prolonged
mental activity.
• When it binds to a specific receptor in the brain,
adenosine sets in motion a signal transduction
pathway that results in reduced brain activity,
which usually means drowsiness.
CAFFEINE AND ADENOSINE
• Caffeine has a 3-dimensional structure similar to
adenosine and is able to bind to the adenosine
receptor.
• Because its binding does not activate the receptor,
caffeine functions as a antagonist of adenosine
signaling, with the result that the brain stays active.
Caffeine
Adenosine
CAFFEINE
• Because caffeine has bound to the adenosine
receptor, the adenosine has little effect, and the
person stays awake.
• The binding of caffeine to the adenosine receptor,
however, is a reversible reaction. In time, the
caffeine molecules come off the adenosine
receptors in the brain, allowing adenosine to bind
once again.
ADDITIONAL EFFECTS OF CAFFEINE
• In addition to competing with adenosine for a
membrane receptor, caffeine blocks the enzyme
cAMP phosphodiesterase.
• This enzyme breaks down cAMP, which is a second
messenger in the pathway that turns glycogen into
sugar which is then released into the bloodstream.
• Can you see how caffeine increases the “fight or
flight” response?