Bài giảng Biology - Chapter 11: Cell Communication

Chapter 11Cell CommunicationOverview: The Cellular InternetCell-to-cell communicationIs absolutely essential for multicellular organismsBiologistsHave discovered some universal mechanisms of cellular regulationFigure 11.1Concept 11.1: External signals are converted into responses within the cellEvolution of Cell SignalingYeast cellsIdentify their mates by cell signaling factorReceptor Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type.1 Mating. Binding of the factors to     receptors induces changes      in the cells that     lead to their     fusion. New a/ cell. The nucleus of the fused cell includes all the genes from the a and a cells.23 factorYeast cell,mating type aYeast cell,mating type a/aaFigure 11.2Signal transduction pathwaysConvert signals on a cell’s surface into cellular responsesAre similar in microbes and mammals, suggesting an early originLocal and Long-Distance SignalingCells in a multicellular organismCommunicate via chemical messengersAnimal and plant cellsHave cell junctions that directly connect the cytoplasm of adjacent cellsPlasma membranesPlasmodesmatabetween plant cellsGap junctionsbetween animal cellsFigure 11.3(a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.Figure 11.3(b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.In local signaling, animal cellsMay communicate via direct contactIn other cases, animal cellsCommunicate using local regulators(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.(b) Synaptic signaling. A nerve cell releases neurotransmitter molecules  into a synapse, stimulating the  target cell.Local regulator diffuses through extracellular fluidTarget cellSecretoryvesicleElectrical signalalong nerve celltriggers release ofneurotransmitterNeurotransmitter diffuses acrosssynapseTarget cellis stimulatedLocal signalingFigure 11.4 A BIn long-distance signalingBoth plants and animals use hormonesHormone travelsin bloodstreamto target cells (c) Hormonal signaling. Specialized  endocrine cells secrete hormones  into body fluids, often the blood.  Hormones may reach virtually all  body cells.Long-distance signalingBloodvesselTargetcellEndocrine cellFigure 11.4 CThe Three Stages of Cell Signaling: A PreviewEarl W. SutherlandDiscovered how the hormone epinephrine acts on cellsSutherland suggested that cells receiving signals went through three processesReceptionTransductionResponseEXTRACELLULARFLUIDReceptorSignal moleculeRelay molecules in a signal transduction pathway Plasma membraneCYTOPLASMActivationof cellularresponseFigure 11.5Overview of cell signalingReception1Transduction2Response3Concept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shapeThe binding between signal molecule (ligand)And receptor is highly specificA conformational change in a receptorIs often the initial transduction of the signalIntracellular ReceptorsIntracellular receptorsAre cytoplasmic or nuclear proteinsSignal molecules that are small or hydrophobicAnd can readily cross the plasma membrane use these receptorsHormone(testosterone)EXTRACELLULARFLUIDReceptorproteinDNAmRNANUCLEUSCYTOPLASMPlasmamembraneHormone-receptorcomplexNew proteinFigure 11.6Steroid hormonesBind to intracellular receptors1 The steroid hormone testosterone passes through the plasma membrane. The bound proteinstimulates thetranscription ofthe gene into mRNA.4 The mRNA istranslated into aspecific protein.5 Testosterone bindsto a receptor proteinin the cytoplasm,activating it.2 The hormone-receptor complexenters the nucleusand binds to specific genes.3Receptors in the Plasma MembraneThere are three main types of membrane receptorsG-protein-linkedTyrosine kinasesIon channelG-protein-linked receptorsG-protein-linkedReceptorPlasma MembraneEnzymeG-protein(inactive)CYTOPLASMCellular responseActivatedenzymeActivatedReceptorSignal moleculeInctivateenzymeSegment thatinteracts withG proteinsGDPGDPGTPGTPP iSignal-binding siteFigure 11.7GDPReceptor tyrosine kinasesSignalmoleculeSignal-binding siteaCYTOPLASMTyrosinesSignal moleculeHelix in the MembraneTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrDimerReceptor tyrosinekinase proteins(inactive monomers)PPPPPPTyrTyrTyrTyrTyrTyrPPPPPPCellularresponse 1Inactiverelay proteinsActivatedrelay proteinsCellularresponse 2Activated tyrosine-kinase regions(unphosphorylateddimer)Fully activated receptortyrosine-kinase(phosphorylateddimer)6 ATP 6 ADPFigure 11.7Ion channel receptorsCellularresponseGate openGate closeLigand-gatedion channel receptorPlasma MembraneSignalmolecule(ligand)Figure 11.7Gate closedIonsConcept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cellMultistep pathwaysCan amplify a signalProvide more opportunities for coordination and regulationSignal Transduction PathwaysAt each step in a pathwayThe signal is transduced into a different form, commonly a conformational change in a proteinProtein Phosphorylation and DephosphorylationMany signal pathwaysInclude phosphorylation cascadesIn this processA series of protein kinases add a phosphate to the next one in line, activating itPhosphatase enzymes then remove the phosphatesSignal moleculeActiveproteinkinase1Activeproteinkinase2Activeproteinkinase3Inactiveprotein kinase1Inactiveprotein kinase2Inactiveprotein kinase3InactiveproteinActiveproteinCellularresponseReceptorPPPATPADPADPADPATPATPPPPPPPActivated relaymoleculeiPhosphorylation cascadeP PiiPA phosphorylation cascadeFigure 11.8 A relay moleculeactivates protein kinase 1.12 Active protein kinase 1transfers a phosphate from ATPto an inactive molecule ofprotein kinase 2, thus activatingthis second kinase. Active protein kinase 2then catalyzes the phos-phorylation (and activation) ofprotein kinase 3.3 Finally, active proteinkinase 3 phosphorylates aprotein (pink) that brings about the cell’s response tothe signal.4 Enzymes called proteinphosphatases (PP)catalyze the removal ofthe phosphate groupsfrom the proteins, making them inactiveand available for reuse.5Small Molecules and Ions as Second MessengersSecond messengersAre small, nonprotein, water-soluble molecules or ionsCyclic AMP Cyclic AMP (cAMP)Is made from ATPFigure 11.9O–OOONOOOOPPPPPPOOOOOOHCH2NH2NH2NH2NNNNNNNNNNNOOOATPCh2CH2OOHOHPOOH2OHOAdenylyl cyclasePhoshodiesterasePyrophosphateCyclic AMPAMPOHOHOiMany G-proteinsTrigger the formation of cAMP, which then acts as a second messenger in cellular pathwaysATPGTPcAMPProteinkinase ACellular responsesG-protein-linkedreceptorAdenylylcyclaseG proteinFirst messenger(signal moleculesuch as epinephrine)Figure 11.10Calcium ions and Inositol Triphosphate (IP3)Calcium, when released into the cytosol of a cellActs as a second messenger in many different pathwaysCalcium is an important second messengerBecause cells are able to regulate its concentration in the cytosolEXTRACELLULARFLUIDPlasmamembraneATPCYTOSOLATPCa2+pumpCa2+pumpCa2+pumpEndoplasmicreticulum (ER)NucleusMitochondrionKeyHigh [Ca2+]Low [Ca2+]Figure 11.11Other second messengers such as inositol triphosphate and diacylglycerolCan trigger an increase in calcium in the cytosolFigure 11.12321 IP3 quickly diffuses throughthe cytosol and binds to an IP3–gated calcium channel in the ERmembrane, causing it to open.4 The calcium ionsactivate the nextprotein in one or moresignaling pathways.6 Calcium ions flow out ofthe ER (down their con-centration gradient), raisingthe Ca2+ level in the cytosol.5 DAG functions asa second messengerin other pathways. Phospholipase C cleaves aplasma membrane phospholipidcalled PIP2 into DAG and IP3. A signal molecule bindsto a receptor, leading toactivation of phospholipase C.EXTRA-CELLULARFLUIDSignal molecule(first messenger)G proteinG-protein-linkedreceptorVariousproteinsactivatedEndoplasmicreticulum (ER)Phospholipase CPIP2 IP3 (second messenger)DAGCellularresponseGTPCa2+(second messenger)Ca2+IP3-gatedcalcium channelConcept 11.4: Response: Cell signaling leads to regulation of cytoplasmic activities or transcriptionCytoplasmic and Nuclear ResponsesIn the cytoplasmSignaling pathways regulate a variety of cellular activitiesCytoplasmic response to a signalFigure 11.13Glucose-1-phosphate(108 molecules)GlycogenActive glycogen phosphorylase (106)Inactive glycogen phosphorylaseActive phosphorylase kinase (105)Inactive phosphorylase kinaseInactive protein kinase AActive protein kinase A (104)ATPCyclic AMP (104)Active adenylyl cyclase (102)Inactive adenylyl cyclaseInactive G proteinActive G protein (102 molecules)Binding of epinephrine to G-protein-linked receptor (1 molecule)TransductionResponseReceptionOther pathwaysRegulate genes by activating transcription factors that turn genes on or offReceptionTransductionResponsemRNANUCLEUSGenePActivetranscriptionfactorInactivetranscriptionfactorDNAPhosphorylationcascadeCYTOPLASMReceptorGrowth factorFigure 11.14Fine-Tuning of the ResponseSignal pathways with multiple stepsCan amplify the signal and contribute to the specificity of the responseSignal AmplificationEach protein in a signaling pathwayAmplifies the signal by activating multiple copies of the next component in the pathwayThe Specificity of Cell SignalingThe different combinations of proteins in a cellGive the cell great specificity in both the signals it detects and the responses it carries outPathway branching and “cross-talk”Further help the cell coordinate incoming signalsResponse 1 Response 4Response 5Response 2Response 3SignalmoleculeCell A. Pathway leads to a single responseCell B. Pathway branches, leading to two responsesCell C. Cross-talk occurs between two pathwaysCell D. Different receptorleads to a different responseActivationor inhibitionReceptorRelaymoleculesFigure 11.15Signaling Efficiency: Scaffolding Proteins and Signaling ComplexesScaffolding proteinsCan increase the signal transduction efficiencySignalmoleculeReceptorScaffoldingproteinThreedifferentproteinkinasesPlasmamembraneFigure 11.16Termination of the SignalSignal response is terminated quicklyBy the reversal of ligand binding