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Transcript
Cell Communication Cellular Communication by direct cell-cell contact Cellular Communication (a) Communicating cell junctions. Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (b) Cell-cell recognition. “Cell phone” Figure 11.3 Cellular Communication — Cellular Communication via chemical messengers 1. Release: initiator cell secretes (exocytosis) a chemical messenger (signal molecules). Reception: messenger molecules bind to receptors (binding proteins) on target cells. Transduction: binding of signal molecule to receptor causes a change in the structure and activity of the receptor protein. Response: the altered receptor protein initiates a change in the enzymatic and/or transcriptional activity of the target cell. 2. 3. 4. EXTRACELLULAR FLUID PLASMA MEMBRANE 2 Reception CYTOPLASM 3 Transduction Receptor Relay molecules in a signal transduction pathway Signal molecule 4 Response Activation of cellular response Figure 11.5 Major Classes of Biochemical Signal Molecules I. Amino acid origin a) b) c) d) II. growth factor, cytokine) diffuses to nearby target cells. 3. Endocrine: the messenger (hormone) diffuses into the bloodstream to travel to target cells all over the body. 4. Exocrine: the messenger (pheromone) diffuses outside of the organism’s body to travel to another organism. Tyrosine family of amines I = iodine Amino acids Modified amino acids — bioamines Oligopeptides Proteins Fatty acid origin a) b) III. Derived from cholesterol — steroids Derived from arachidonic acid — prostaglandins Dissolved gases a) b) c) Heyer Chemical Messengers & Receptors the messenger One cell releases a molecule 1. Synapse: (neurotransmitter) diffuses (messenger) that initiates a across a small gap between a neuron and its target cell. change in another cell by binding to a protein receptor 2. Paracrine: the messenger (local regulator, paracrine factor, on that target cell. Note iodine Nitric oxide (NO) Carbon monoxide (CO) Ethylene (H 2C=CH 2) 1 Cell Communication Mechanisms of Messenger Action • Hydrophilic signal molecules — most amino acid class – Water soluble. – Short half-life: minutes – Do not enter target cells. Act as ligand by binding to protein receptor on cell surface. • Lipophilic signal molecules — most fatty acid class – Water insoluble. Must be transported in plasma by carrier proteins. – Carrier proteins also protect hormone from degradation. Half-life longer: 1–2 hours. – Released from carrier protein to diffuse across cell membrane into target cells. Act by binding to intracellular protein receptors. Signal transduction pathways via second messengers Act as cofactors/coenzymes to modulate intracellular enzyme activity Signal molecule (first messenger) Steroids Mechanisms of Hydrophilic Signal Molecule Action • Hydrophilic signal molecules — most amino acid class – Water soluble. – Short half-life: minutes – Do not enter target cells. Act as ligand by binding to protein receptor on cell surface. 1. Since the signal molecule (first messenger) does not enter the cell, the receptor/ligand complex causes a second messenger to be produced or released within the cell. 2. This second messenger acts as a coenzyme/cofactor to regulate cellular enzymes fi change the activity of the cell. Common second messengers Act as cofactors/coenzymes to modulate intracellular enzyme activity ++ 1. Ca NH NH 2 N O Receptor Activated relay molecule (second messenger) 2. cAMP O N O – O P O P O P O Ch 2 O OOO- Inactive enzyme Active enzyme Heyer ATP 3. IP3 4. DAG Phospholipid (PIP 2) in membrane bilayer N N 2 N N Adenylyl cyclase N N Figure 11.9 Tryptophan family of amines CH 2 O O O P Pyrophosphate O- O P Pi OH OH OH Phospholipase C Cyclic AMP Inisotol triphosphate (IP 3) + Diacylglycerol (DAG) 2 Cell Communication 1. G-protein mediated 2. Tyrosine kinase 3. Receptor-ion channels G-protein-mediated Membrane Receptors Signal-binding site Segment that interacts with G proteins 1. 2. 3. 4. 5. 6. 7. G-protein-linked Receptor Signal molecule binds receptor. Receptor-ligand bind G-protein; G-protein releases GDP. G-protein binds GTP; receptor releases G-protein–GTP. G-protein–GTP moves along membrane to inactive enzyme. Enzyme is activated; second messenger is produced. G-protein hydrolyzes P i from GTP; enzyme releases G-protein–GDP. Enzyme inactivated again. Go to #1. Activated Receptor Plasma Membrane Signal molecule Inactivated enzyme GDP G-protein (inactive) CYTOPLASM Enzyme GDP GTP Activated enzyme GTP Inactivated enzyme Figure 11.7 Membrane Receptor Types GDP Pi Cellular response Membrane protein activity mediated via GDP/GTP-binding proteins (G-proteins). Second messenger: cyclic-AMP Second messengers: IP3 / DAG / Ca++ Tyrosine Kinase Receptors Receptor-ion channels Signal molecule (ligand) Gate closed Ligand-gated ion channel receptor Ions Plasma Membrane – Direct: receptor is the gate. – Indirect: receptor opens/closes separate gate protein via G-proteins. Gate open Cellular response Gate closes • Kinase (“enzyme activation enzyme”): phosphorylase • Tyrosine kinase: phosphate added to tyrosine residues of enzyme proteins Heyer • Chemically-mediated ion gates • Signal molecule binds receptor; gated channel opens or closes • Opening gates causes voltage change in cell. – Na + gate: depolarizes – K+ or Cl – gate: hyperpolarizes Figure 11.7 3 Cell Communication Cascade reactions amplify signal Phosphorylation Cascade Scaffolding proteins or cytoskeleton may hold group of cascade enzymes in a complex. Signal molecule Activated relay molecule Receptor Active protein kinase 1 Inactive protein kinase 2 2 Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. ATP PP Inactive protein kinase 3 5 Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. P Active protein kinase 2 ADP Pi Figure 11.8 1 A relay molecule activates protein kinase 1. ATP Pi de sca ca on lati ory ph os Ph Inactive protein kinase 1 3 Active protein kinase 2 then catalyzes the phosphorylation (and activation) of protein kinase 3. Active protein kinase 3 ADP PP Inactive protein ATP Pi PP ADP P 4 Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. P Active Cellular protein response Intracellular Receptors for Lipophilic Signal Molecules 1. Steroid diffuses across membrane into cell 2. Intracellular receptor/steroid complex binds to DNA 3. Transcription factor — turns genes on/off 4. Change nature of the cell (Longer-lasting effect) Reception • One epinephrine signal molecular momentarily binding to the membrane receptor • Results in the production of 100,000,000 glucose-1-phosphate molecules in the cell. Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Inactive G protein Active G protein (10 2 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (10 2) ATP Cyclic AMP (10 4) Inactive protein kinase A Active protein kinase A (10 4) Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (10 6) Response Glycogen Glucose-1-phosphate (108 molecules) Figure 11.13 Mechanisms of Messenger Action • Hydrophilic signal molecules — most amino acid class – Bind to membrane receptors on cell surface – Primary effect: turn enzymes on/off Æ D activity of cell. – Secondary effect: enzymes may produce or activate transcription Growth factor Reception factors Æ turn genes on/off. Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive Active transcription transcription factor P factor DNA Response Gene NUCLEUS Mechanisms of Messenger Action • Hydrophilic signal molecules — most amino acid class – Bind to membrane receptors on cell surface – Primary effect: turn enzymes on/off Æ D activity of cell. – Secondary effect: enzymes may produce or activate transcription factors Æ turn genes on/off. • Lipophilic signal molecules — most fatty acid class – Bind to intracellular receptors in cytoplasm or nucleoplasm – Primary effect: turn genes on/off Æ D nature of cell. – Secondary effect: gene expression may produce or activate enzymes Æ turn metabolic pathways on/off. Heyer mRNA Figure 11.14 Modulation of signal effect •Priming (upregulation) Signal bindsÆ more receptors synthesized Ø more hormone can bind cell •Desensitization (downregulation) Prolonged exposure to high signal molecule levels can reduce receptor expression. * Downregulation may be avoided by pulsatile secretion of the messenger. •Receptor-mediated endocytosis Receptor-ligand complex internalized on vesicle to enhance duration of effect. 4 Cell Communica,on • Dendrites: increase surface area of cell body to receive signals. Electrochemical communication Rapid signaling to specific targets • Cell body: location of nucleus and most organelles. Neuron — cell extends axon to release • Axon: conducts electrochemical impulses. signal molecule at local site • Termini: transmit message to target cell. Neuron: A Nerve Cell Action Potential Neuron Requirements by voltage-gated ion channels Function requires: 1. Membrane potential: – Voltage (millivolts) across plasma membrane 2. Excitability: – The ability to undergo rapid changes in membrane potential in response to stimuli 3. Conduction: – Propagation of a series of excitations along the plasma membrane 4. Transmission: – Release and reception of signal molecules (neurotransmitters) 1 Na+ channels open • 2 Na+ rushes in (making inside positive) Na+ channels close. K+ channels open • 3 K+ K+ rushes out (making it negative) channels close. Na+ / K+ pumps resegregate ions. c.f., Fig. 48.10 Conduction of electrochemical signals in neuron axons • Nerve impulse is a series of action potentials propagated in sequence down the neuron. • Nerves are NOT wires! • Nerve impulses are NOT electricity! • Only the axons of neurons conduct the nerve impulse. • Initiated at the hillock, Fig. 48.11 Heyer • Propagate toward the axon terminus 5 Cell Communica,on Transmission: Synapses & Local Signaling • Synaptic terminals secrete signal molecules – neurotransmitter — e.g. acetylcholine • NT binds to receptors on postsynaptic cell. Fig. 48.12 Synaptic Transmission: release of signal molecule Synaptic Transmission: Reception • Action potentials conducted down axon to terminus. • Voltage-Gated Ca2+ channels open. – Ca2+ rapidly enters terminus • (down concentration and charge gradient). – Ca2+ acts as cofactor for enzymes to trigger rapid fusion of synaptic vesicles è exocytosis of neurotransmitter (NT) into synaptic cleft. • NT release is rapid because many vesicles form fusion-complexes at “docking sites.” Synaptic Transmission: release & reception • NT receptors open ion channels, allowing in Na+ – this initiates a response in the target cell • Released NTs diffuse across synaptic cleft. • NT (ligand) binds to specific receptor proteins in postsynaptic cell membrane. • Chemically-regulated gated ion channels open. – If Na+ gates è depolarization è stimulation. – If K+ or Cl– gates è hyperpolarization è inhibition. • Neurotransmitter inactivated to end transmission. Neurotransmitters • Different types used by different neurons. • NTs are broken down & recycled by enzymes. – dopamine, serotonin, endorphins, even NO • They can excite or inhibit transmission. • Chemicals (e.g., LSD, insecticides, opiates) – mimic neurotransmitters – block neurotransmitters – block receptor sites – block breakdown enzymes Fig. 48.16 Heyer 6