cell communication ap biology. types of signaling paracrine – local – cell secretes a signal...
TRANSCRIPT
Cell CommunicationCell Communication
AP BiologyAP Biology
Types of SignalingTypes of Signaling
Paracrine Paracrine – local – cell secretes a signal that – local – cell secretes a signal that binds to neighboring cell receptors binds to neighboring cell receptors (growth factors + attraction of immune cells)(growth factors + attraction of immune cells)
SynapticSynaptic – nerves produce neurotransmitters – nerves produce neurotransmitters that bind to receptors on an adjacent cellthat bind to receptors on an adjacent cell
HormoneHormone – chemical released into blood and – chemical released into blood and binds to receptors on distant cellsbinds to receptors on distant cells
Direct communicationDirect communication – diffusion of chemicals – diffusion of chemicals through plasmosdesmata or gap junctions through plasmosdesmata or gap junctions and direct contact in cell to cell recognition and direct contact in cell to cell recognition (immune cells)(immune cells)
Receptor Binding OutcomesReceptor Binding Outcomes
Signal binds to the receptor and Signal binds to the receptor and changes its shapechanges its shape
May cause receptors to aggregate and May cause receptors to aggregate and lead to endocytosislead to endocytosis
May open gated channelsMay open gated channels May turn on genes (growth factors and May turn on genes (growth factors and
steroid hormones)steroid hormones) sets off a series of chemical reactionssets off a series of chemical reactions May lead to cell division or cell deathMay lead to cell division or cell death Stimulate cell secretionStimulate cell secretion Changing cell shapeChanging cell shape Set off muscle contractionSet off muscle contraction
1 1 endocytosisendocytosis
2 opening a 2 opening a channelchannel
3 + 4 3 + 4 turning on a turning on a genegene
5 activate 5 activate enzymesenzymes
11 22 33
44
55
Signal TransductionSignal TransductionChanging a signal from 1 form to anotherChanging a signal from 1 form to another
Signal Transduction PathwaySignal Transduction Pathway – all the steps – all the steps from the signal binding to the end resultfrom the signal binding to the end result
A cascade of activation of enzymesA cascade of activation of enzymes Leads to amplification of the signal Leads to amplification of the signal
because one active enzyme activates a because one active enzyme activates a bunch of others amplification videobunch of others amplification video• May directly activate enzymes that activate May directly activate enzymes that activate
other enzymesother enzymes• May activate second messengers that activate May activate second messengers that activate
enzymesenzymes
Amplification of the SignalAmplification of the Signal
How do you convert an electrical to a How do you convert an electrical to a chemical signal?chemical signal?
Example of Signal Transduction
Two Major Types of Signal Two Major Types of Signal Transduction ReceptorsTransduction Receptors
G-Protein ReceptorsG-Protein Receptors - Lead to activation of - Lead to activation of G proteins – Activate one enzyme – which G proteins – Activate one enzyme – which then sets off the cascade or opens an ion then sets off the cascade or opens an ion channel – may set off multiple reactionschannel – may set off multiple reactions
Tyrosine Kinase ReceptorsTyrosine Kinase Receptors - Lead to - Lead to activation of tyrosine kinases – triggers activation of tyrosine kinases – triggers multiple signal transduction pathways at multiple signal transduction pathways at onceonce- Growth factors work through this path- Growth factors work through this path
G Protein Linked ReceptorsG Protein Linked ReceptorsAn OverviewAn Overview
800 human genes that encode G Protein Linked 800 human genes that encode G Protein Linked Receptors (4% of the human genome)Receptors (4% of the human genome)
50% of all medicines target these receptors50% of all medicines target these receptors They are used for vision (convert light to cellular They are used for vision (convert light to cellular
signals), smell, mood regulators (serotonin and signals), smell, mood regulators (serotonin and dopamine), activate immune cells, control blood dopamine), activate immune cells, control blood pressure, heart rate, and activate tumor growth pressure, heart rate, and activate tumor growth and metastasisand metastasis
They bind to hormones (350 different kinds for They bind to hormones (350 different kinds for hormones), odors, neurotransmitters, hormones), odors, neurotransmitters, pheromones)pheromones)
G-Protein Linked ReceptorsG-Protein Linked ReceptorsHow they workHow they work
When a ligand binds to a receptor – the receptor When a ligand binds to a receptor – the receptor changes shape and attaches to a G-Protein.changes shape and attaches to a G-Protein.
This changes the shape of the G-protein allowing This changes the shape of the G-protein allowing GTP to displace GDP GTP to displace GDP
When GDP is attached its inactive/ when GTP is When GDP is attached its inactive/ when GTP is attached it activeattached it active
A piece of the G protein falls off and the remaining A piece of the G protein falls off and the remaining piece translocates in the membrane until it hits piece translocates in the membrane until it hits another proteinanother protein
The active G protein activates the protein it hitsThe active G protein activates the protein it hits
To inactivate it – the G protein itself clips the To inactivate it – the G protein itself clips the phosphate off of GTP and it becomes GDP which phosphate off of GTP and it becomes GDP which causes the receptor to go back to its inactive form causes the receptor to go back to its inactive form and resets everything. (part of the G protein is a and resets everything. (part of the G protein is a phosphatase)phosphatase)
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
video showing general G-protein mechanisms
G protein receptors and IP3
Videos Showing the Actions of G-protein linked receptors
Tyrosine Kinase ReceptorsTyrosine Kinase ReceptorsAn OverviewAn Overview
90 different genes to encode this 90 different genes to encode this type of receptortype of receptor
Mostly receive growth factors, Mostly receive growth factors, cytokines, and hormonescytokines, and hormones
Examples: Insulin receptor, Examples: Insulin receptor, receptors that stimulate the growth receptors that stimulate the growth of blood vesselsof blood vessels
What’s a Kinase?What’s a Kinase?
An enzyme that adds a POAn enzyme that adds a PO44-- to to
another molecule to activate it (it another molecule to activate it (it usually gets the phosphate from usually gets the phosphate from
ATP)ATP)
Tyrosine Kinase ReceptorsTyrosine Kinase ReceptorsHow They WorkHow They Work
The interior portion of the receptor is a tyrosine The interior portion of the receptor is a tyrosine kinase which phosphorylates tyrosine amino acids kinase which phosphorylates tyrosine amino acids on itself using ATPon itself using ATP
The receptor has 2 halves – each with a series of The receptor has 2 halves – each with a series of tyrosinestyrosines
When the ligand binds – 2 halves of the receptor When the ligand binds – 2 halves of the receptor aggregateaggregate
The tyrosines are phosphorylated and activated – The tyrosines are phosphorylated and activated – each side phosphorylates the other sideeach side phosphorylates the other side
Relay molecules bind to the phosphorylated Relay molecules bind to the phosphorylated tyrosines and get activatedtyrosines and get activated
To inactivate it – phosphatases in the cytoplasm To inactivate it – phosphatases in the cytoplasm and stuck in the cell membrane cleave the and stuck in the cell membrane cleave the phosphates off of the tyrosine kinase receptorphosphates off of the tyrosine kinase receptor
Activation by Tyrosine Kinase Activation by Tyrosine Kinase ReceptorsReceptors
Video on Tyrosine Kinase receptor
activation
Long version describing action of
tyrosine kinase receptors
How the Insulin Receptor Works
Second MessengersSecond Messengers Small – non-protein molecules that can activate Small – non-protein molecules that can activate
a large amount of enzymesa large amount of enzymes Ex. cAMP and calcium, IP3, DAGEx. cAMP and calcium, IP3, DAG Best advantage – small so can diffuse much Best advantage – small so can diffuse much
quicker than enzymes which are bigquicker than enzymes which are big G protein and tyrosine kinase receptors both G protein and tyrosine kinase receptors both
can work via 2can work via 2ndnd messengers messengers
For cAMP:For cAMP: when the receptor is activated when the receptor is activated• it activates adenylate cyclase which creates cAMP it activates adenylate cyclase which creates cAMP
from ATPfrom ATP• The cAMP activates a cascade of kinasesThe cAMP activates a cascade of kinases
ATP and cAMPATP and cAMP
Using Ca++ as a 2Using Ca++ as a 2ndnd Messenger Messenger
Ligand activates receptor which Ligand activates receptor which activates enzymes that cause the activates enzymes that cause the formation of IP3 (from phospholipids)formation of IP3 (from phospholipids)
IP3 opens gated channels and lets Ca IP3 opens gated channels and lets Ca out of the SERout of the SER
Ca binds to Calmodulin protein which Ca binds to Calmodulin protein which activates a host of other kinasesactivates a host of other kinases
Calcium as a Calcium as a 22ndnd
messengermessenger
End Result of Kinase ActivationEnd Result of Kinase Activation Activate many molecules of a single Activate many molecules of a single
enzyme type to make a lot of one enzyme type to make a lot of one productproduct
Activate multiple enzymes to make Activate multiple enzymes to make multiple productsmultiple products
Turn on genes to make a specific Turn on genes to make a specific product by protein synthesisproduct by protein synthesis• Kinase activates a transcription factor Kinase activates a transcription factor
(growth factors work this way)(growth factors work this way)
Receptors that Turn on GenesReceptors that Turn on Genes
Growth factors activate transription Growth factors activate transription factors through a cascade of factors through a cascade of phosphorylationphosphorylation
Steroid hormones – bind to a Steroid hormones – bind to a cytosolic receptor that then cytosolic receptor that then translocates into the nucleus and translocates into the nucleus and binds to the DNA turning on genesbinds to the DNA turning on genes
Action of Steroids Hormones on Intracellular Receptors
How does the same signal have How does the same signal have different effects in different cells?different effects in different cells?
What proteins the receptor activates inside the cellWhat proteins the receptor activates inside the cell The receptor may be different (it would have the same The receptor may be different (it would have the same
shaped pocket)shaped pocket)
Action of Adrenaline on Action of Adrenaline on Different CellsDifferent Cells
Skeletal Muscle – breaks down glycogenSkeletal Muscle – breaks down glycogen Smooth muscle of lungs – relaxes itSmooth muscle of lungs – relaxes it Smooth muscle of BV – contracts itSmooth muscle of BV – contracts it Heart – beat fasterHeart – 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 When using proteins as the relay molecules, how do you make the molecules, how do you make the reactions happen efficiently in the reactions happen efficiently in the
cytoplasm?cytoplasm? Scaffold Proteins: Scaffold Proteins:
Large proteins Large proteins that hold other that hold other
kinases togetherkinases together Proteins don’t Proteins don’t have to diffuse – have to diffuse – they are already they are already
right thereright there
Examples of Drugs that work by Examples of Drugs that work by blocking or activating receptorsblocking or activating receptors
Blood Pressure Medication – blocks the Blood Pressure Medication – blocks the angiotensin II receptor (angiotensin causes angiotensin II receptor (angiotensin causes the muscle around blood vessels to the muscle around blood vessels to contract)contract)
Anti-histamines block the H1 receptor for Anti-histamines block the H1 receptor for histamineshistamines
Morphine binds to the Morphine binds to the
endorphin receptor whichendorphin receptor which
releases endorphins which releases endorphins which
prevent painprevent painNote: all 3 are G protein receptorsNote: all 3 are G protein receptors
What Happens when receptors are What Happens when receptors are exposed to high amounts of ligand or exposed to high amounts of ligand or
exposed to ligand for a prolonged time?exposed to ligand for a prolonged time? The receptors are moved to the The receptors are moved to the
inside of the cell inside of the cell OROR They aren’t linked to the G protein They aren’t linked to the G protein
anymore anymore OROR They are destroyed by lysosomesThey are destroyed by lysosomes
End Result:End Result:
Decreased sensitivity to the ligandDecreased sensitivity to the ligand
Cause of both drug addiction and type Cause of both drug addiction and type II DiabetesII Diabetes