1. Cell Communication
AP Biology

2. 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)

4. 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

5. 1 2 3 4 5 1 endocytosis 2 opening a channel 3 + 4 turning on a gene
5 activate enzymes

7. Signal Transduction Changing a signal from 1 form to another
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

9. Amplification of the Signal

10. How do you convert an electrical to a chemical signal?
Example of Signal Transduction
How do you convert an electrical to a chemical signal?

11. 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

12. 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)

13. 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)

16. 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

17. 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

18. What’s a Kinase?
An enzyme that adds a PO4- to another molecule to activate it (it usually gets the phosphate from ATP)

19. 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

20. Activation by Tyrosine Kinase Receptors
Video on Tyrosine Kinase receptor activation
Long version describing action of tyrosine kinase receptors
How the Insulin Receptor Works

21. 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

22. ATP and cAMP

24. 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

25. Calcium as a 2nd messenger

26. 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)

27. 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

29. 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)

30. 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

31. Proteins don’t have to diffuse – they are already right there
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

32. 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

33. 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