Transcript Cell Communication

AP Biology
Types of Signaling
 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
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
– 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
 Signal Transduction Pathway
 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
 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
 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
 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
 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
 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
 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
nd
2
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
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
 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
Action of Steroids Hormones on
Intracellular Receptors
How does the same signal have different
effects in different cells?
 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
 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 and
an increase in blood pressure
Relax smooth muscle in lung and 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
 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
 They aren’t linked to the G protein anymore
OR
OR
 They are destroyed by lysosomes
End Result:
Decreased sensitivity to the ligand
Cause of both drug addiction and type II Diabetes