Download Ch 11 - cell communication

Chapter 11
Cell Communication
Who do cells talk to?
What do cells have to say to
one another?
Communication
• Direct – like passing a note in class
• Over a distance – like emailing each other
• Broad, long distance – posting a status on
facebook
3 major ways cells use communication signals:
• Electromagnetic signals
– Light  phototropism of plants
– Gravity  gravitropism of plants
• Mechanical signals
– Touch  thigmotropism of plants
• Chemical signals
– Using chemicals  hormones, enzymes, ions,
vitamins, minerals, etc.
Signal transduction
pathways convert
signals on a cell’s
surface into cellular
responses
 factor
Receptor
1
Exchange
of mating
Factors

a
a factor
Yeast cell,
Yeast cell,
mating type a
mating type 
(sticky note
communication)
2
Mating
3
New a/
cell
Communication between mating yeast

a
a/
• Signaling
molecules
evolved in
prokaryotes
and were
modified
later in
eukaryotes
1
Individual rodshaped cells
2 Aggregation in
process
http://www.youtube.co
m/watch?v=GScyw3am
mmk&feature=fvw
0.5 mm
3
Spore-forming
structure
(fruiting body)
•
Slime molds
aggregate to form
reproductive
organs; otherwise,
live solitary lives
Fruiting bodies
• Chemical
messengers
how cells in a
multicellular
organism
communicate
• Local
signaling
Plasma membranes
Gap junctions
between animal cells
(a) Cell junctions
(b) Cell-cell recognition
Plasmodesmata
between plant cells
• Local regulators - messenger molecules that
travel only short distances (email
communication)
• Hormones are used for long-distance signaling
in plants and animals (facebook response)
Long-distance signaling
Local signaling
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Target cell
Secreting
cell
Local regulator
diffuses through
extracellular fluid
(a) Paracrine signaling general
Endocrine cell
Neurotransmitter
diffuses across
synapse
Secretory
vesicle
Target cell
is stimulated
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
(b) Synaptic signaling specific
(c) Hormonal signaling –
general/specific
• Sutherland – 3 stages of cell signaling
– Reception
– Transduction
– Response
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
Reception: A signal molecule binds to a receptor
protein, causing it to change shape
• The binding between a ligand (signal
molecule) and receptor is specific, like a lock
and key fit
• Receptor shape change is often the initial
transduction of the signal
• Most signal receptors are plasma membrane
proteins
• Ligands rarely enter the cell, simply initiate the
message
Receptors in the Plasma Membrane
• There are three main types of membrane
receptors:
– G protein-coupled receptors
– Receptor tyrosine kinases
– Ion channel receptors
• G proteincoupled
receptor
works with
the help of a
G protein
Signaling-molecule binding site
• The G protein
acts as an
on/off switch:
Segment that
If GDP is
interacts with
bound to G
G proteins
protein, it is
inactive
G protein-coupled receptor
Plasma
membrane
G protein-coupled
receptor
Activated
receptor
Signaling molecule
GDP
CYTOPLASM
GDP
Enzyme
G protein
(inactive)
GTP
2
1
Activated
enzyme
GTP
GDP
GTPase
Cellular response
3
http://www.youtube.com/watch?v=U6uHotlXvPo&feature=related
4
When action is complete, ligand is released,
enzyme inactivates, g-protein and receptor ready to go again
Pi
Inactive
enzyme
• Explain why G-protein regulated pathways shut
down rapidly in the absence of a signal
molecule
• What determines whether a cell is a target cell
for a particular signal molecule
• Receptor tyrosine kinases - membrane receptors that act
as enzymes to attach phosphates to tyrosines (AA)
– ‘Phosphorylates’ the tyrosines
• Why? Energy continuation depends on “holding patterns”
for molecules (make it, break it, make it again)
– ATP  ADP + P  AMP + P + P
• Can trigger multiple signal transduction pathways at
once
• Ex: growth factors
Ligand-binding site
Signaling
molecule (ligand)
Signaling
molecule
 Helix
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
CYTOPLASM
Dimer
1
2
Activated relay
proteins
Tyr
Tyr
Tyr
Tyr
P Tyr
P Tyr
Tyr
Tyr
P
6 ATP
Activated tyrosine
kinase regions
6 ADP
Tyr
Tyr
P Tyr
Tyr
P
Tyr
P Tyr
P Tyr
Tyr
P
P
P
P
Tyr P
Tyr
Fully activated receptor
tyrosine kinase
Inactive
relay proteins
3
4
Cellular
response 1
Cellular
response 2
Human Growth Hormone activation
• Ligand-gated ion channel
receptor acts as a gate to
an ion channel
• The gate allows only
specific ions, such as Na+
or Ca2+, through the
channel
1 Signaling
molecule
(ligand)
Ligand-gated
ion channel receptor
2
• Ex: muscle contraction is
regulated by sodium ions
• http://www.youtube.com/wa
tch?v=LdmceBXkna8&feat
ure=related
Gate
closed
Ions
Plasma
membrane
Gate open
Cellular
response
3
Gate closed
• What determines whether a signal molecule
binds to a membrane-surface receptor or an
intracellular receptor?
Intracellular Receptors
• Found in the cytosol or
nucleus of target cells
• Small or hydrophobic (nonpolar) chemical messengers
cross the membrane and
activate receptors
– ex. Steroids and puberty
development
• An activated hormone-receptor
complex can act as a transcription
factor, turning on specific genes
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
Signal Transduction Pathways
• The relay molecules (receptor to response) are
mostly proteins
• The receptor activates a protein, which
activates another, and so on, until the protein
producing the response is activated
• At each step, the signal is transduced
(changed) into a different form, usually a
protein shape change
• Original “signal” is not changed by these
reactions!!
Signaling molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
What does protein kinase do?
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
ADP
Pi
PP
Inactive
protein kinase
3
Pi
What does PP do?
PP – protein phosphatase
P
Active
protein
kinase
2
ATP
ADP
Active
protein
kinase
3
PP
Inactive
protein
P
ATP
P
ADP
Pi
PP
Active
protein
Cellular
response
Small Molecules and Ions as Second Messengers
• The extracellular signal molecule that binds to
the receptor is a pathway’s “first messenger”
• Second messengers - small, nonprotein,
water-soluble molecules or ions
• The “go-between guy”
• Cyclic AMP and calcium ions are common
second messengers
First messenger
Adenylyl
cyclase
G protein
G protein-coupled
Receptor
GTP
ATP
cAMP
Second
messenger
Protein
kinase A
Cellular responses
Calcium Ions and
Inositol Triphosphate
(IP3)
• Ca2+ act as a
second messenger
in many pathways
• Calcium - can
regulate its
concentration
EXTRACELLULAR
FLUID
Plasma
membrane
Ca2+ pump
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
Endoplasmic
reticulum (ER)
– Muscle
contraction
ATP
Key
High [Ca2+]
Low [Ca2+]
Ca2+
pump
EXTRACELLULAR
FLUID
Ca2+ and IP3 in signaling pathways
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
PIP2
Phospholipase C
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Various
proteins
activated
Ca2+
Ca2+
(second
messenger)
Cellular
responses
Nuclear and Cytoplasmic Responses
• Regulation of one or more cellular activities
• The response may occur in the cytoplasm or in
the nucleus
• Many signaling pathways regulate the
synthesis of enzymes or other proteins, by
turning genes on or off in the nucleus
• The final activated molecule may function as a
transcription factor
Growth factor
Gene activation
by a growth factor
Reception
Receptor
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
mRNA
Reception
Other
pathways
regulate
the activity
of
enzymes
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 (104)
Inactive phosphorylase kinase
Active phosphorylase kinase (105)
Glycogen
breakdown
by
epinephrine
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106)
Response
Glycogen
Glucose-1-phosphate
(108 molecules)
Fine-Tuning of the Response
• Multistep pathways have two important
benefits:
– Signal amplification the signal – the # of
activated products is greater than the
preceeding step
– Contributes to the specificity of the response
• Only one respose possible
• Different cell types have
different proteins
(FACEBOOK POST)
• different proteins allow cells
to detect and respond to
different signals
• same signal can have
different effects in cells with
different proteins and
pathways
• Ex: human growth hormone
affects different cells
differently
Signaling
molecule
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.
Activation
or inhibition
Response 4
Cell C. Cross-talk occurs
between two pathways.
Response 5
Cell D. Different receptor
leads to a different response.
• Scaffolding proteins are large relay proteins to
which other relay proteins are attached
• Scaffolding proteins can increase the signal
transduction efficiency by grouping together
different proteins involved in the same pathway
Fig. 11-18
Signaling
molecule
Plasma
membrane
Receptor
Three
different
protein
kinases
Scaffolding
protein
Termination of the Signal
• Inactivation mechanisms are an essential
aspect of cell signaling
• When signal molecules leave the receptor, the
receptor reverts to its inactive state – WHY is
this important?
• So, what if a cell does NOT receive the
message?
Diseases associated with Cell Signaling problems
• Obesity
• Cancer
• Alzheimer’s
• Parkinson’s