* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Cell A.
Survey
Document related concepts
Cell growth wikipedia , lookup
Cell nucleus wikipedia , lookup
NMDA receptor wikipedia , lookup
Purinergic signalling wikipedia , lookup
Cellular differentiation wikipedia , lookup
Extracellular matrix wikipedia , lookup
Organ-on-a-chip wikipedia , lookup
Hedgehog signaling pathway wikipedia , lookup
Cell membrane wikipedia , lookup
Protein phosphorylation wikipedia , lookup
Cytokinesis wikipedia , lookup
Endomembrane system wikipedia , lookup
Biochemical cascade wikipedia , lookup
G protein–coupled receptor wikipedia , lookup
List of types of proteins wikipedia , lookup
Transcript
Ch. 11: Cell Communication Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ch. 11: Cell Communication • Coordinate activities – Universal mechanisms among all living cells – Provides evidence for evolutionary relatedness of all life. – Ligand – chemical signals • water soluble • too large to cross the plasma membrane • Signal-transduction Pathway – • signal on cell’s surface - converts into a specific cellular response - a series of steps Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.2 Communication between mating yeast cells factor 1 Exchange of Receptor mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type. a Yeast cell, mating type a a factor Yeast cell, mating type 2 Mating. Binding of the factors to receptors induces changes in the cells that lead to their fusion. a 3 New a/ cell. The nucleus of the fused cell includes all the genes from the a and cells. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings a/ Direct Contact: • Plant cells – thru plasmodesmata • Animal cells - between membrane-bound cell surface molecules. • importance - embryonic development, immune response. • Ex. growth factors- stimulate nearby target cells to grow/multiply. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.3 Communication by direct contact between cells Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes. (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Local or long distance: 1. paracrine signaling - direct contact transmitting cells release local regulators • cell junctions connect to the cytoplasm of adjacent cells. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.4 Local and long-distance cell communication in animals Local signaling Target cell Secreting cell Secretory vesicle Local regulator diffuses through extracellular fluid (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Local: 2. synaptic signaling – neurotransmitter - diffuses across a synapse to a very close cell (target cell) -neurotransmitter stimulates the target cell Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.4 Local and long-distance cell communication in animals Local signaling Target cell Secreting cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Secretory vesicle Local regulator diffuses through extracellular fluid (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. Target cell is stimulated (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Long distance: 3. hormonal signaling – long distance signaling; plants and animals • plant hormone - ethylene (C2H4) – 6 atom hydrocarbon passes through cell walls. – promotes fruit ripening – regulates growth • Mammal hormone - Insulin – regulates blood sugar levels in mammals – a protein with thousands of atoms. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.4 Local and long-distance cell communication in animals Local signaling Long-distance signaling Target cell Secreting cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Secretory vesicle Local regulator diffuses through extracellular fluid (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. Endocrine cell Target cell is stimulated Blood vessel Hormone travels in bloodstream to target cells Target cell (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells. 3 stages of cell signaling: • 1. reception • 2. transduction • 3. response Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.5 Overview of cell signaling EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 1. Reception • a chemical signal binds to a cellular protein receptor – cell’s surface or inside cell. • Target cell recognizes the signal molecule – due to a complimentary shape • Receptor undergoes a shape change – allowing interaction with other molecules Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.5 Overview of cell signaling EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction Receptor Signal molecule Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2. Transduction: A Signal-Transduction Pathway • Initiation - Receptor protein changes • Converts signal to a form that brings about a specific cellular response • Ex. Epinephrine binding to a receptor protein in a liver cell’s plasma membrane – leads to activation of glycogen phosphorylase Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.5 Overview of cell signaling EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction Receptor Relay molecules in a signal transduction pathway Signal molecule Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Response – Transduction signal triggers a specific cellular response such as: – catalysis by an enzyme – rearrangement of the cytoskeleton – activation of specific genes in the nucleus Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.5 Overview of cell signaling EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Hormone receptors • are intercellular • their ligands are nonpolar – travel between lipids in plasma membrane – steroids, thyroid hormones Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.6 Steroid hormone interacting with an intracellular receptor Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex hormone testosterone passes through the plasma membrane. 2 Testosterone binds to a receptor protein in the cytoplasm, activating it. 3 The hormonereceptor complex enters the nucleus and binds to specific genes. DNA mRNA NUCLEUS 1 The steroid 4 The bound protein stimulates the transcription of the gene into mRNA. New protein 5 The mRNA is translated into a specific protein. CYTOPLASM Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings I. Reception: 3 major types of membrane receptors: 1. G-protein-linked receptors 2. Tyrosine kinase receptors 3. Ion-channel receptors. • Most signal receptors are plasma membrane proteins. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.7 Exploring Membrane Receptors Signal-binding site G-PROTEIN-LINKED RECEPTORS Segment that interacts with G proteins G-protein-linked receptor Plasma Membrane Activated receptor Signal molecule GDP CYTOPLASM G-protein (inactive) Enzyme GDP GTP Activated enzyme GTP GDP Pi Cellular response Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Inactive enzyme 1. G-protein-linked receptor • a receptor protein associated with a G protein - G protein acts as an on/off switch. • GDP - bound to the G protein (inactive) • ligand binds to the G protein receptor, • G protein binds GTP (active) • G protein dissociates from receptor • diffuses along the membrane • binds to an enzyme, altering its activity. • enzyme triggers next step leading to cellular response. – • G protein can also act as GTPase enzyme - hydrolyze GTP to GDP. turns G protein off. – leaves the enzyme Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.7 Exploring Membrane Receptors Signal-binding site G-PROTEIN-LINKED RECEPTORS - embryonic development. -Vision and smell in humans depend on these proteins. -Bacterial infections - cholera and botulism interfere with Gprotein function. Segment that interacts with G proteins •binds many epinephrine and neurotransmitters. G-protein-linked receptor Plasma Membrane Activated receptor Signal molecule GDP CYTOPLASM G-protein (inactive) Enzyme GDP GTP Activated enzyme GTP GDP Pi Cellular response Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Inactive enzyme TYROSINE KINASE RECEPTORs RECEPTOR TYROSINE KINASES Signal-binding site Signal molecule Signal molecule Helix in the Membrane Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) CYTOPLASM Dimer Activated relay proteins Tyr Tyr P Tyr Tyr Tyr P Tyr Tyr Tyr P Tyr 6 ATP Activated tyrosinekinase regions (unphosphorylated dimer) 6 ADP Tyr P Tyr P P Tyr Tyr P P Tyr Tyr P Tyr P P Tyr Tyr P Fully activated receptor tyrosine-kinase (phosphorylated dimer) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Inactive relay proteins Cellular response 1 Cellular response 2 2. tyrosine-kinase receptor – • work in pairs – dimers • Ligands bind to two receptors - dimerization – kinase - an enzyme that catalyzes the transfer of phosphate groups – P from 6ATP’s + tyrosine tails – Activates cellular response Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings TYROSINE KINASE RECEPTORs RECEPTOR TYROSINE KINASES- coordinate cell growth/reproduction. Signal-binding site Signal molecule Signal molecule Helix in the Membrane Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) CYTOPLASM Dimer Activated relay proteins Tyr Tyr P Tyr Tyr Tyr P Tyr Tyr Tyr P Tyr 6 ATP Activated tyrosinekinase regions (unphosphorylated dimer) 6 ADP Tyr P Tyr P P Tyr Tyr P P Tyr Tyr P Tyr P P Tyr Tyr P Fully activated receptor tyrosine-kinase (phosphorylated dimer) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Inactive relay proteins Cellular response 1 Cellular response 2 3. Ligand-gated ion channel • Ligand binds to receptor protein – gate opens - allow ions in, ex. Na+ or Ca2+ – ligand dissociates - channel closes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ion Channel Receptors Ex. nervous system: •Ions trigger electrical signals •propagate down the receiving cell Signal molecule (ligand) Gate Gate close Closed Ions Ligand-gated ion channel receptor Plasma Membrane Gate open Cellular response Gate close Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings ION CHANNEL RECEPTORS II. Transduction: • Cascade of relay signals from receptors to relay molecules in the cell – greatly amplifies the signal – few signal molecules - large cellular response. – mostly proteins – signal is transduced into a different form • often by a conformational change – by transferring a P - phosphorylation. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.8 A phosphorylation cascade abnormal activity of one of the kinases can cause abnormal cell growth/reproduction and contribute to the development of cancer Signal molecule Receptor Activated relay molecule Inactive protein kinase 1 1 A relay molecule activates protein kinase 1. 2 Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. Active protein kinase 1 Inactive protein kinase 2 ATP ADP Pi 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. 3 Active protein kinase 2 then catalyzes the phosphorylation (and activation) of protein kinase 3. P Active protein kinase 2 ATP ADP Pi Active protein kinase 3 PP Inactive protein P ATP P ADP Pi PP Ossilation between phosphorylation and dephosphorylation Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 4 Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. Active protein Cellular response Second Messengers – involved in signal transduction pathways 1. cyclic AMP NH2 N N O O O N N – O P O P O P O Ch2 O O O NH2 NH2 O Pyrophosphate P Pi O CH2 Phoshodiesterase ATP O HO P O CH2 Requires constant supply of ligand to remain in the cyclic form activated receptor activates adenylyl cyclaseconverts ATP to cAMP. Maintains high levels of cellular activity Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings O H2O OH Cyclic AMP Figure 11.9 Cyclic AMP N N O O O P O N N N N Adenylyl cyclase O OH OH N N OH OH AMP 1. cAMP Figure 11.10 cAMP as a second messenger in a G-protein-signaling pathway First messenger (signal molecule such as epinephrine) G protein G-protein-linked receptor Adenylyl cyclase GTP ATP “Fight or flight” hormone from adrenal medulla Second cAMP messenger Protein kinase A Cellular responses Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cholera toxin modifies G protein in intestinal cells, cAMP is constantly active, causing intestinal cells to release salts, dehydration occurs Signal Transduction Scenario 3.Sugar activates a G protein-linked receptor on the tongue stimulating adenylyl cyclase to produce cAMP. cAMP activates protein kinase A which closes K+ channels and causes Ca 2+ ions to enter the cell. The influx of Ca2+ causes the release of a neurotransmitter form the tongue & provides the “sweet” taste from some candy. 6.Activation of a G-protein-linked receptor stimulates adenylyl cyclase to convert ATP to cAMP. cAMP activates protein kinase A which initiates a phosphorylation cascade that ends with the phosphorylation of glycogen phosphorylase and releases glucose from glycogen. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2. Ca2+ (2nd messenger) • Animal cells – • Increases may cause contraction of muscle cells Plant cells – – increase triggers responses • pathway for greening in response to light. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signal Transduction Scenerio 4.Sunlight is detected by a plant cell which opens Ca2+ channels in the plasma membrane. The Ca2+ ions activate protein kinase 2 which phosphorylates transcription factors for de-etiolation genes (genes that cause greening of the plant). 7.The neurotransmitter acetylcholine activates a ligandgated ion channel causing Na+ ions to enter a muscle cell. Because the muscle cell is now “charged,” Ca2+ ions are released, which bind to a muscle protein allowing a muscle to contract. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.11 The maintenance of calcium ion concentrations in an animal cell – a secondary messenger EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion Nucleus CYTOSOL Ca2+ pump ATP Ca2+ Endoplasmic reticulum (ER) pump Key High [Ca2+] Low [Ca2+] Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ca2+ concentration in the cytosol is usually much lower than that in the extracellular fluid and ER. Protein pumps in the plasma membrane and the ER membrane, driven by ATP move Ca2+ from the cytosol into the extracellular fluid and into the lumen of the ER. Mitochondrial pumps, driven by chemiosmosis, move Ca2+ into mitochondria when the calcium level in the cytosol rises significantly. Function: Muscle cell contractions, cell division, growth factors, neurotransmitters. 3. Diacylglycerol (DAG) and inositol trisphosphate (IP3). • DAG and IP3 are created when a phospholipase cleaves membrane phospholipid PIP2 (inositol) • phospholipase - activated by G protein or tyrosine-kinase receptor. • IP3 activates a gated-calcium channel, releasing Ca2+ from the ER. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.12 Calcium and IP3 in signaling pathways 1 A signal molecule binds to a receptor, leading to activation of phospholipase C. EXTRACELLULAR FLUID 2 Phospholipase C cleaves a plasma membrane phospholipid called PIP2 into DAG and IP3. 3 DAG functions as a second messenger in other pathways. Signal molecule (first messenger) G protein DAG GTP PIP2 G-protein-linked receptor Phospholipase C IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) Various proteins activated Ca2+ CYTOSOL 4 IP3 quickly diffuses through the cytosol and binds to an IP3– gated calcium channel in the ER membrane, causing it to open. Cellular responses Ca2+ (second messenger) 5 Calcium ions flow out of the ER (down their concentration gradient), raising the Ca2+ level in the cytosol. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 6 The calcium ions activate the next protein in one or more signaling pathways. Signal Transduction Scenerio 1.Activation of a tyrosine-kinase receptor causes phopholipase C to cleave PIP2 forming IP3 and DAG from the cell membrane. IP3 then binds to a ligand-gated ion channel on the ER causing the release of calcium ions, which bind to calmodulin & causes the cytoskeleton to change shape. 8.The binding of a sperm to an egg initiates a G protein pathway that releases IP3 & DAG. This releases Ca2+ ion from the ER which cause the cortical reaction and allow for the formation of the fertilization envelope. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings III. Response: A signal (ligand) • Opens or closes ion channels. • regulates enzyme activity • act as transcription factors - turn specific genes on/off (nucleus) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.13 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine Reception Binding of epinephrine to G-protein-linked receptor (1 molecule) Amplifies the hormonal signal Transduction Inactive G protein Active G protein (102 molecules) Activates about 100 G protein molecules Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose-1-phosphate (108 molecules) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.14 Nuclear responses to a signal: the activation of a specific gene by a growth factor Growth factor Local regulator Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor P Response DNA Gene NUCLEUS Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings mRNA Signal Transduction Scenerio 2.Activation of a steroid hormone receptor causes the hormone/receptor complex to travel into the nucleus and turn on genes (initiate transcription) needed for making muscle protein. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.15 The specificity of cell signaling Signal molecule Receptor Relay molecules Response 1 Response 2 Response 3 Cell A. Pathway leads to a single response Cell B. Pathway branches, leading to two responses Activation or inhibition Response 4 Cell C. Cross-talk occurs between two pathways Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Response 5 Cell D. Different receptor leads to a different response Scaffolding proteins – Rather than relying on diffusion of large relay molecules – pathways are linked together physically by scaffolding – enhances speed, accuracy, and efficiency Signal molecule Plasma membrane Receptor Scaffolding protein Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Three different protein kinases