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 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

How do you convert an electrical to a chemical 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 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

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 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