Download Chapter 11: Cell Communication 10/7/2015

10/7/2015
Chapter 11:
Cell Communication
1. Overview of Cell Communication
2. Receptors: Receiving the Signal
3. Signal Transduction
4. Responding to the Signal
1. Overview of
Cell Communication
Chapter Reading – pp. 211-214
Cell Communication in Microbes
 factor
Receptor
1
Exchange
of mating
factors

a
• intercellular signaling
occurs in single-celled
microbes and has likely
been around a long time
a factor
1 Individual
Yeast
cell,
rod-shaped
matingcells
type 
Yeast cell,
mating type a
2
Mating

a
Aggregation
in progress
0.5 mm
3 Spore-forming
structure
(fruiting body)
3
New a/ cell
2.5 mm
a/
Fruiting bodies
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Soluble Signals in
Multicellular Organisms
3 basic types:
1) endocrine
• signal acts from a distance
• hormones are “endocrine”
2) paracrine
• signal acts locally, on nearby cells
3) autocrine
• signal acts on source cell (“self-stimulation”)
Endocrine
Signaling
Long-distance signaling
Endocrine cell
Soluble molecular
signals a released that
travel throughout a
multicellular organism
via circulatory system
• hormones released by
glands in the
endocrine system
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
(c) Hormonal signaling
Local Signaling
• release of soluble signal molecules that act locally
Paracrine signaling
Synaptic signaling
Target cell
Secreting
cell
Local regulator
diffuses through
extracellular fluid
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across
synapse
Secretory
vesicle
Target cell
is stimulated
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Autocrine Signaling
Autocrine signals activate receptors
on the cell producing the signal
Signaling through Cell-Cell Contact
Plasma membranes
Gap junctions
between animal cells
Plasmodesmata
between plant cells
• signals can be
passed between
cells via junctions
linking the cytosol
(a) Cell junctions
• membrane-bound
ligands can bind
to receptors on
adjacent cells
(b) Cell-cell recognition
Stages of Cell Signaling
Signaling between cells occurs in 4 general
steps:
1) Signal molecule “released” from source cell
2) Signal molecule received by target cell
3) Signal relayed to cell interior
4) Signal reaches target, cell responds*
*Cell responses include changes in gene expression or
changes in the activity of proteins or other macromolecules
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Responding to the Signal
The trick is getting the signal received
transmitted to the target within the cell:
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
2. Receptors:
Receiving the Signal
Chapter Reading – pp. 214-218
Common Types of Receptors
Listed below are common types of membrane
receptor proteins that transmit signal to the
interior of a cell when bound to ligand:
G protein-coupled receptors (GPCRs)
• associated with intracellular G proteins
Receptor Tyrosine Kinases (RTKs)
• phosphorylate intracellular tyrosine residues
Ion Channel Receptors
• receptors that also function as ion channels
Steroid Hormone Receptors
• intracellular receptors that bind hormones
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Kinases & Transcription Factors
Key targets of most signaling pathways are
various kinases & transcription factors (TFs).
Kinases:
• enzymes that “phosphorylate” (add a phosphate to)
very specific substrates
• phosphorylate either serine or threonine residues
(serine/threonine kinases) or tyrosines (tyrosine kinases)
• can activate or inhibit substrate
Transcription Factors:
• proteins that regulate transcription of specific genes
there are also important phosphatases (remove phosphates)
G Protein-Coupled Receptors
These are integral
membrane proteins
that bind a specific
ligand on the
exterior of the cell
and interact with
G proteins on the
cytoplasmic side of
the membrane.
Signaling-molecule binding site
Segment that
interacts with
G proteins
G proteins are
activated to transmit
signal when GPCR
binds ligand
G protein-coupled receptor
G Proteins
• inactive when bound to GDP, active when bound to GTP
Plasma
membrane
G protein-coupled
receptor
Activated
receptor
Signaling molecule
Inactive
enzyme
GDP
CYTOPLASM
GDP
Enzyme
G protein
(inactive)
GTP
2
1
Activated
enzyme
GTP
GDP
Pi
Cellular response
3
4
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Receptor Tyrosine Kinases
Ligand-binding site
Signaling
molecule
(ligand)
 Helix
Signaling
molecule
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor
tyrosine
kinase proteins
CYTOPLASM
Tyr
Tyr
Tyr
Tyr
Dimer
1
2
Activated relay
proteins
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
6 ATP
6 ADP
Activated
tyrosine
kinase regions
P Tyr
P Tyr
P Tyr
Gate
closed
Ions
Plasma
membrane
Gate open
Cellular
response
3
Tyr
P Tyr
P Tyr
P Tyr
P
P
P
Tyr P
Tyr
Tyr
P
P
Cellular
response 1
Cellular
response 2
Inactive
relay
proteins
4
Ligand-gated
ion channel receptor
2
Tyr
Fully activated
receptor
tyrosine kinase
3
1 Signaling
molecule
(ligand)
Tyr
Gate closed
Ion Channel
Receptors
Many ion channels are gated,
i.e., they contain a “gate”
which can block the channel.
By default, the gate may be
closed (or open) only to open
(or close) when a soluble
signaling molecule is bound
to the channel.
Steroid Hormone
Receptors
Steroid hormones are
released into the blood from
distant sites.
They are lipid soluble
(hydrophobic), and pass
directly through membranes.
The receptors they bind are
intracellular receptors which
become active upon binding.
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
New protein
CYTOPLASM
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3. Signal Transduction
Chapter Reading – pp. 218-222
What is Signal Transduction?
The process by which a signal received at the
cell surface is transmitted to the intracellular
target of that signal.
Common signal transduction pathways involve:
Phosphorylation Cascades
• sequential phosphorylation of molecules
Second messengers:
• cyclic AMP (cAMP)
• inositol triphosphate (IP3)
• calcium
Cascades of Phosphorylation
Signaling
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
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Cyclic AMP
Cyclic AMP is adenosine monophosphate in
which the phosphate group is covalently bound
to two carbons in the sugar ribose.
• produced upon activation of the enzyme
Adenylyl Cyclase
Adenylyl cyclase
Phosphodiesterase
Pyrophosphate
P
Pi
ATP
AMP
cAMP
Cyclic AMP & Protein Kinase A
First messenger
Adenylyl
cyclase
G protein
G protein-coupled
receptor
• some G proteins
activate adenylyl
cyclase and
cAMP production
GTP
ATP
cAMP
Second
messenger
Protein
kinase A
• cAMP in turn
activates Protein
Kinase A which
phosphorylates
key targets
Cellular responses
Calcium as a
2nd Messenger
EXTRACELLULAR
FLUID
Plasma
membrane
Ca2+ pump
ATP
Mitochondrion
Calcium ions are
generally maintained at
a lower concentration
in the cytosol relative
to the extracellular
environment and the
endoplasmic reticulum
• release of calcium
stores from ER or
outside the cell is
part of some
signaling pathways
Nucleus
CYTOSOL
Ca2+
pump
Endoplasmic
reticulum (ER)
ATP
Ca2+
pump
Key
High [Ca2+]
Low [Ca2+]
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Inositol Triphosphate & Calcium
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)
Various
proteins
activated
Ca2+
Cellular
responses
Ca2+
(second
messenger)
CYTOSOL
4. Responding to the Signal
Chapter Reading – pp. 223-230
Growth factor
Reception
Receptor
Phosphorylation
cascade
Changes in
Gene
Expression
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Signal transduction
frequently changes
gene expression by
activating
(or inhibiting)
transcription factors
Gene
NUCLEUS
mRNA
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Amplification
of Signals
Reception
Binding of epinephrine to G protein-coupled receptor (1 molecule)
Transduction
Inactive G protein
This example shows
how binding to a
single molecule of
ligand results in a
108-fold amplification
of the original signal
• this example also
shows how signal
transduction results
in the activation of a
type of enzyme in
the cytoplasm
Signaling
molecule
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)
Variety in Signaling
Response
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.
Different cell types can
respond in different
ways to the same
external signal.
• the same receptor-ligand
complex can be linked to
different intracellular signal
transduction pathways in
different cells
Activation
or inhibition
Response 4
Cell C. Cross-talk occurs
between two pathways.
Response 5
Cell D. Different receptor
leads to a different response.
Apoptosis & Cell Signaling…
Apoptosis is
also known as
“Programmed
Cell Death”.
Ced-9
protein (active)
inhibits Ced-4
activity
Mitochondrion
Apoptosis can
be activated in
a variety of
ways
including the
binding of an
extracellular
signal.
Receptor
for deathsignaling
molecule
Ced-4 Ced-3
Inactive proteins
(a) No death signal
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…Apoptosis & Cell Signaling
Ced-9
(inactive)
Cell
forms
blebs
Deathsignaling
molecule
Active
Ced-4
Active
Ced-3
Activation
cascade
Other
proteases
Nucleases
(b) Death signal
Apoptosis is part of Normal
Development
1 mm
Interdigital tissue
During embryonic development, many cells must
die by apoptosis in order for a structure or organ
to form properly.
• loss of webbing between toes and fingers
• loss of neurons during brain and nerve development
Key Terms for Chapter 11
• endocrine, paracrine, autocrine signals, ligand
• G protein receptors, kinase, phosphatase
• receptor tyrosine kinases, ion channel receptors
• signal transduction, signal cascade
• 2nd messengers, cyclic AMP, protein kinase A
• inositol triphosphate (IP3), phospholipase C
• signal amplification
• apoptosis
Relevant
Chapter
Questions
1-5, 7, 8, 10
11