Transcript Cell Communication

Cell Communication
AP Biology
Types of Signaling
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Paracrine – local – cell secretes a signal that
binds to neighboring cell receptors
(growth factors + attraction of immune cells)
Synaptic – nerves produce neurotransmitters
that bind to receptors on an adjacent cell
Hormone – chemical released into blood and
binds to receptors on distant cells
Direct communication – diffusion of
chemicals through plasmosdesmata or gap
junctions and direct contact in cell to cell
recognition (immune cells)
Receptor Binding Outcomes
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Signal binds to the receptor and
changes its shape
May cause receptors to aggregate and
lead to endocytosis
May open gated channels
May turn on genes (growth factors and
steroid hormones)
sets off a series of chemical reactions
May lead to cell division or cell death
Stimulate cell secretion
Changing cell shape
Set off muscle contraction
1
2
3
4
5
1
endocytosis
2 opening a
channel
3+4
turning on a
gene
5 activate
enzymes
Signal Transduction
Changing a signal from 1 form to another
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Signal Transduction Pathway – all the steps
from the signal binding to the end result
A cascade of activation of enzymes
Leads to amplification of the signal
because one active enzyme activates a
bunch of others amplification video
• May directly activate enzymes that activate
other enzymes
• May activate second messengers that activate
enzymes
Amplification of the Signal
Example of Signal Transduction
How do you convert an electrical to a
chemical signal?
Two Major Types of Signal
Transduction Receptors
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G-Protein Receptors - Lead to activation of
G proteins – Activate one enzyme – which
then sets off the cascade or opens an ion
channel – may set off multiple reactions
Tyrosine Kinase Receptors - Lead to
activation of tyrosine kinases – triggers
multiple signal transduction pathways at
once
- Growth factors work through this path
G Protein Linked Receptors
An Overview
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800 human genes that encode G Protein Linked
Receptors (4% of the human genome)
50% of all medicines target these receptors
They are used for vision (convert light to cellular
signals), smell, mood regulators (serotonin and
dopamine), activate immune cells, control blood
pressure, heart rate, and activate tumor growth
and metastasis
They bind to hormones (350 different kinds for
hormones), odors, neurotransmitters,
pheromones)
G-Protein Linked Receptors
How they work
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When a ligand binds to a receptor – the receptor
changes shape and attaches to a G-Protein.
This changes the shape of the G-protein allowing GTP
to displace GDP
When GDP is attached its inactive/ when GTP is
attached it active
A piece of the G protein falls off and the remaining
piece translocates in the membrane until it hits
another protein
The active G protein activates the protein it hits
To inactivate it – the G protein itself clips the
phosphate off of GTP and it becomes GDP which
causes the receptor to go back to its inactive form
and resets everything. (part of the G protein is a
phosphatase)
Videos Showing the Actions of
G-protein linked receptors
video showing general G-protein mechanisms
Video showing opening of Calcium Channels by
G-protein receptors
Video showing activation of adenylate cyclase by
G protein receptors
Video showing the action of epineprine on
Gprotein receptors to cause teh breakdown
of glycogen to glucose
G protein receptors and IP3
Tyrosine Kinase Receptors
An Overview
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90 different genes to encode this
type of receptor
Mostly receive growth factors,
cytokines, and hormones
Examples: Insulin receptor,
receptors that stimulate the growth
of blood vessels
What’s a Kinase?
An enzyme that adds a PO4- to
another molecule to activate it (it
usually gets the phosphate from
ATP)
Tyrosine Kinase Receptors
How They Work
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The interior portion of the receptor is a tyrosine
kinase which phosphorylates tyrosine amino acids
on itself using ATP
The receptor has 2 halves – each with a series of
tyrosines
When the ligand binds – 2 halves of the receptor
aggregate
The tyrosines are phosphorylated and activated –
each side phosphorylates the other side
Relay molecules bind to the phosphorylated
tyrosines and get activated
To inactivate it – phosphatases in the cytoplasm
and stuck in the cell membrane cleave the
phosphates off of the tyrosine kinase receptor
Activation by Tyrosine Kinase
Receptors
Video on Tyrosine
Kinase receptor
activation
Long version
describing action of
tyrosine kinase
receptors
How the Insulin
Receptor Works
Second Messengers
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Small – non-protein molecules that can
activate a large amount of enzymes
Ex. cAMP and calcium, IP3, DAG
Best advantage – small so can diffuse
much quicker than enzymes which are big
G protein and tyrosine kinase receptors
both can work via 2nd messengers
For cAMP: when the receptor is activated
• it activates adenylate cyclase which creates
cAMP from ATP
• The cAMP activates a cascade of kinases
ATP and cAMP
Using Ca++ as a 2nd Messenger
Ligand activates receptor which
activates enzymes that cause the
formation of IP3 (from phospholipids)
 IP3 opens gated channels and lets Ca
out of the SER
 Ca binds to Calmodulin protein which
activates a host of other kinases
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Calcium as a
2nd
messenger
End Result of Kinase Activation
Activate many molecules of a single
enzyme type to make a lot of one
product
 Activate multiple enzymes to make
multiple products
 Turn on genes to make a specific
product by protein synthesis
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• Kinase activates a transcription factor
(growth factors work this way)
Receptors that Turn on Genes
Growth factors activate transription
factors through a cascade of
phosphorylation
 Steroid hormones – bind to a
cytosolic receptor that then
translocates into the nucleus and
binds to the DNA turning on genes
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Action of Steroids Hormones on
Intracellular Receptors
How does the same signal have
different effects in different cells?
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What proteins the receptor activates inside the cell
The receptor may be different (it would have the same
shaped pocket)
Action of Adrenaline on
Different Cells
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Skeletal Muscle – breaks down glycogen
Smooth muscle of lungs – relaxes it
Smooth muscle of BV – contracts it
Heart – beat faster
Blood Vessels
Lungs
Alpha Adrenergic Receptors
Beta Adrenergic Receptors
G protein activates phospholipase C
G protein activates adenylate
cyclase
2nd messenger IP3
2nd messenger cAMP
Ion channel in SER opened, release
Calcium
Calcium response blocked
Causes contraction of smooth muscle Relax smooth muscle in lung and
and an increase in blood pressure
can breath easier
When using proteins as the relay
molecules, how do you make the
reactions happen efficiently in the
cytoplasm?
Scaffold Proteins:
Large proteins
that hold other
kinases together
Proteins don’t
have to diffuse –
they are already
right there
Examples of Drugs that work by
blocking or activating receptors
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Blood Pressure Medication – blocks the
angiotensin II receptor (angiotensin
causes the muscle around blood vessels to
contract)
Anti-histamines block the H1 receptor for
histamines
Morphine binds to the
endorphin receptor which
releases endorphins which
prevent pain
Note: all 3 are G protein receptors
What Happens when receptors are
exposed to high amounts of ligand or
exposed to ligand for a prolonged time?
The receptors are moved to the
inside of the cell
OR
 They aren’t linked to the G protein
anymore
OR
 They are destroyed by lysosomes
End Result:
Decreased sensitivity to the ligand
Cause of both drug addiction and type
II Diabetes
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