(a) Communicating cell junctions. by direct cell-cell contact lasma membranes 1. Direct cell contact. Vesicle-mediated 3. Chemical messengers (b) Cell-cell recognition. Gap junctions between animal cells lasmodesmata between plant cells Figure 11.3 via extracellular vesicles via chemical messengers Target cells Endosome Initiator (secreting) cell Multivesicular Element Budding of microvesicles and/or exocytosis of exosomes transport mras & miras to recipient cells Secretory vesicles (chemical messenger) Modified from Graça Raposo, and Willem Stoorvogel J Cell Biol 013;00:373-383 via chemical messengers 1. Release: initiator cell secretes (exocytosis) a chemical messenger (signal molecules).. Reception: messenger molecules bind to receptors (binding s) on target cells. 3. Transduction: binding of signal molecule to receptor causes a change in the structure and activity of the receptor. 4. Response: the altered receptor initiates a change in the enzymatic and/or transcriptional activity of the target cell. EXTRACELLULAR FLUID LASMA MEMBRAE CYTOLASM Reception 3 Transduction 4 Response Relay molecules in a signal transduction pathway Activation of cellular response Figure 11.5 Chemical Messengers & s 1. Synapse: the messenger One cell releases a molecule (neurotransmitter) diffuses (messenger) that initiates a across a small gap between a change in another cell by neuron and its target cell. binding to a receptor. aracrine: the messenger (local on that target cell. regulator, paracrine factor, 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. Heyer 1
Mechanisms of Messenger Action Amino acids; bioamines; oligopeptides; s Water soluble. Short half-life: minutes Do not enter target cells. Act as ligand by binding to receptor on cell surface. Lipophilic signal molecules most fatty acid class Steroids; prostaglandins Water insoluble. Must be transported in plasma by carrier s. Carrier s also protect hormone from degradation. Half-life longer: 1 hours. Released from carrier to diffuse across cell membrane into target cells. Act by binding to intracellular receptors. Mechanisms of Hydrophilic Signal Molecule Action Water soluble. Short half-life: minutes Do not enter target cells. Act as ligand by binding to 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.. This second messenger acts as a co/cofactor to regulate cellular s change the activity of the cell. Membrane roteins The binding between a signal molecule (ligand) and receptor is highly specific A shape change in a receptor is often the initial transduction of the signal β -adrenergic receptors Ligand Signal transduction pathways via second messengers Act as cofactors/cos to modulate intracellular activity (first messenger) Activated relay molecule (second messenger) lasma membrane Cholesterol Common second messengers Act as cofactors/cos to modulate intracellular activity 1. Ca ++. cam H H O O O Adenylyl cyclase O O O O Ch CH O - O - O - O O O O yrophosphate i O - O OH OH OH AT Cyclic AM Figure 11.9 Membrane Types 1. G- mediated. Tyrosine kinase 3. -ion channels 3. I 3 4. DAG hospholipid (I ) in membrane bilayer hospholipase C Inisotol triphosphate (I 3 ) + Diacylglycerol (DAG) Heyer
i i i Cell Communication G--mediated Membrane s Signal-binding site 1. binds receptor.. -ligand bind G-; G- releases GD. 3. G- binds GT; receptor releases G- GT. 4. G- GT moves along membrane to inactive. 5. Enzyme is activated; second messenger is produced. Segment that 6. G- hydrolyzes i from GT; releases G- GD. interacts with G s 7. Enzyme inactivated again. Go to #1. G--linked lasma Membrane Activated Inactivated Second messenger: cyclic-am CYTOLASM GD G- (inactive) Enzyme Activated GD GT Inactivated Figure 11.7 GT GD i Cellular response Membrane activity mediated via GD/GT-binding s (G-s). Second messengers: I 3 / DAG / Ca ++ Tyrosine Kinase s Kinase ( activation ): phosphorylase Tyrosine kinase: phosphate added to tyrosine residues of s Figure 11.8 hosphorylation Cascade kinase 1 kinase kinase 1 kinase 3 5 Enzymes called phosphatases () catalyze the removal of the phosphate groups from the s, making them inactive and available for reuse. Activated relay molecule AT AD AT kinase AD 1 A relay molecule activates kinase 1. kinase 1 transfers a phosphate from AT to an inactive molecule of kinase, thus activating this second kinase. AT 3 kinase then catalyzes the phosphorylation (and activation) of kinase 3. kinase 3 AD Scaffolding s or cytoskeleton may hold group of cascade s in a complex. hosphorylation cascade 4 Finally, active kinase 3 phosphorylates a (pink) that brings about the cell s response to the signal. Cellular response Cascade reactions amplify signal 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. Reception Binding of epinephrine to G--linked receptor (1 molecule) Transduction G adenylyl cyclase Response G (10 molecules) adenylyl cyclase (10 ) AT kinase A Cyclic AM (10 4 ) phosphorylase kinase kinase A (10 4 ) phosphorylase kinase (10 5 ) glycogen phosphorylase glycogen phosphorylase (10 6 ) Glycogen Glucose-1-phosphate (10 8 molecules) Figure 11.13 Heyer 3
Signal molecule (ligand) Ligand-gated ion channel receptor Gate open -ion channels Gate closed Gate closes Ions lasma Membrane Cellular response Chemically-mediated ion gates binds receptor; gated channel opens or closes Direct: receptor is the gate. Indirect: receptor opens/closes separate gate via G-s. Opening gates causes voltage change in cell. a + gate: depolarizes K + or Cl gate: hyperpolarizes Intracellular s for Lipophilic Signal Molecules 1. Steroid diffuses across membrane into cell. Intracellular receptor/ steroid complex binds to DA 3. Transcription factor turns genes on/off 4. Change nature of the cell (Longer-lasting effect) Figure 11.7 Mechanisms of Messenger Action Bind to membrane receptors on cell surface rimary effect: turn s on/off Δ activity of cell. Secondary effect: s may produce or activate transcription Growth factor Reception factors turn genes on/off. CYTOLASM transcription factor transcription factor DA hosphorylation cascade Transduction Response Gene Mechanisms of Messenger Action Bind to membrane receptors on cell surface rimary effect: turn s on/off Δ activity of cell. Secondary effect: s may produce or activate transcription factors turn genes on/off. Lipophilic signal molecules most fatty acid class Bind to intracellular receptors in cytoplasm or nucleoplasm rimary effect: turn genes on/off Δ nature of cell. Secondary effect: gene expression may produce or activate s turn metabolic pathways on/off. UCLEUS mra Figure 11.14 Modulation of signal effect riming (upregulation) Signal binds more receptors synthesized more hormone can bind cell Desensitization (downregulation) rolonged exposure to high signal molecule levels can reduce receptor expression. Downregulation may be avoided by pulsatile secretion of the messenger. -mediated endocytosis -ligand complex internalized on vesicle to enhance duration of effect. Compound messenger effects Antagonistic: Insulin stimulates lipogenesis; glucagon stimulates lipolysis. Synergistic: Both glucagon and epinephrine receptors cause the production of cam second messenger in the same cell. Complementary: FSH and testosterone stimulate different parts of spermatogenesis. ermissive: Glucocorticoids stimulate the synthesis of s that are regulated by epinephrine. Heyer 4
Electrochemical communication Rapid signaling to specific targets euron cell extends axon to release signal molecule at local site eurons & Specific Long-distance Communication eurotransmitter molecules produced in vesicles by rer & Golgi in Cell Body Vesicles transported along cytoskeleton from Cell Body to Axon Termini eurotransmitter secreted (exocytosis) from Termini into Synapse How does receiving a signal on dendrites result rapidly in releasing signal molecules into synapse? euron Requirements Function requires: 1. Membrane potential: Voltage (millivolts) across plasma membrane. Excitability: The ability to undergo rapid changes in membrane potential in response to stimuli 3. Conduction: ropagation of a series of excitations along the plasma membrane 4. Transmission: Release and reception of signal molecules (neurotransmitters) Membranes of cells are electrically polarized Ion concentration gradients electrical gradient 3 Resting Membrane otential At equilibrium, inside of the cell membrane would have a higher [negative charges] than the outside. otential difference: Magnitude of difference in charge on the sides of the membrane.. Depends upon factors: Ratio of the concentrations of each ion on the sides of the plasma membrane. Specific permeability of membrane to each different ion. Resting membrane potential of most cells ranges from - 65 to 85 mv. Action otential by voltage-gated ion channels 1 a + channels open a + rushes in (making inside positive) a + channels close. K + channels open K + rushes out (making it negative) 3 K + channels close. a + / K + pumps resegregate ions. c.f., Fig. 48.10 Heyer 5
Conduction of electrochemical signals in neuron axons Fig. 48.11 Fig. 48.1 Synaptic Transmission: release of signal molecule Action potentials conducted down axon to terminus. Voltage-Gated Ca + channels open. Ca + rapidly enters terminus (down concentration and charge gradient). Ca + acts as cofactor for s to trigger rapid fusion of synaptic vesicles è exocytosis of neurotransmitter (T) into synaptic cleft. T release is rapid because many vesicles form fusion-complexes at docking sites. Synaptic Transmission: Reception Released Ts (signal molecules) diffuse across synaptic cleft. T (ligand) binds to specific receptor-ion channels in postsynaptic cell membrane. Ligand-gated ion channels open. If a + gates! depolarization! stimulation. If K + or Cl gates! hyperpolarization! inhibition. eurotransmitter inactivated to end transmission. Synaptic Transmission: release & reception T receptors open ion channels, allowing in a + this initiates a response in the target cell Ts are broken down & recycled by s. eurotransmitters Different types used by different neurons. dopamine, serotonin, endorphins, even O They can excite or inhibit transmission. Chemicals (e.g., LSD, insecticides, opiates) mimic neurotransmitters block neurotransmitters block receptor sites block breakdown s Fig. 48.16 Heyer 6