第十一章-细胞通讯-北大陈建国细胞生物学

Cellsignalingcanaffectvirtuallyeveryaspectofcellstructureandfunction:Activationofenzymeactivity;--metabolism,apoptosis,immunologyChangeincytoskeletalorganization;--movement,immunologyChangeinionpermeability;--neuraltransmission,immunologyInitiationofDNAsynthesis;--cellcycle,cellgrowthActivationorrepressionofgeneexpression.--celldifferentiation,developmentChapter11CellSignaling3.Signaltransductionmediatedbythereceptorsonthecellsurface2.Signaltransductionmediatedbythereceptorswithincells1.Overviewofintercellularsignaling4.Signalsthatoriginatefromcontactsbetweenthecellsurfaceandthesubstratum5.Convergence,divergence,andcrosstalkamongdifferentsignalingpathwaysManybacteria,forexample,respondtochemicalsignalsthataresecretedbytheirneighborsandincreaseinconcentrationwithincreasingpopulationdensity—tosuccessfullyinfectthehostQuorumsensing:Allowsbacteriatocoordinatetheirbehavior,includingtheirmotility,antibioticproduction,sporeformation,andsexualconjugationUnicellularorganisms:bacteria,archaea,protozoa,algaeandfungiAlthoughthesecellslargelyleadindependentlives,theycancommunicateandinfluenceoneanother’sbehavior.1.OverviewofintercellularsignalingYeastcellscommunicatewithoneanotherinpreparationformating:whenahaploidindividualisreadytomate,itsecretesapeptidematingfactorthatsignalscellsoftheoppositematingtypetostopproliferatingandpreparetomate.Thesubsequentfusionoftwohaploidcellsofoppositematingtypeproducesadiploidcell,whichcanthenundergomeiosisandgeneratinghaploidcellswithnewassortmentsofgenes.----Tohelpaspeciessurviveinanunpredictedenvironment.UnicellularorganismsCellscommunicatebymeansofhundredsofkindsofsignalmolecules:proteins,smallpeptides,aminoacids,nucleotides,steroids,retinoids(类视黄醇),fattyacidderivatives,anddissolvedgasessuchasnitricoxide(NO)andcarbonmonoxide(CO).1)Secretedsignal-dependentsignaling:mostofthesignalmoleculesarereleasedintotheextracellularspacebyexocytosisfromthesignalingcell.2)Contact-dependentsignaling:transmembraneproteins,importantduringdevelopmentandinimmuneresponses.3)GapJunctions:allowneighboringcellstoshareinformation.Multicellularanimals1)Secretedsignalmolecules-dependentcommunicationEndocrinesignaling:cellssecretesignalmolecules,calledhormones,intothebloodstream,whichcarriesthemoleculesfarandwide,allowingthemtoactontargetcellsthatmaylieanywhereinthebody.Paracrinesignaling:affectsonlycellsinthelocalenvironmentofthesignalingcell.Usually,thesignalingandtargetcellsinparacrinesignalingareofdifferentcelltypes.Forparacrinesignalstoactonlylocally,thesecretedmoleculesmustnotbeallowedtodiffusetoofar;sotheyareoftenrapidlytakenupbyneighboringtargetcells,destroyedbyextracellularenzymes,orimmobilizedbytheextracellularmatrix.Autocrinesignaling:cellsproducesignalsthattheythemselvesrespondto.Cancercells,forexample,oftenusethisstrategytostimulatetheirownsurvivalandproliferationEndocrine,paracrine,andautocrinesignalingdifferaccordingtothedistanceoverwhichthesignalingmoleculeacts.Inendocrinesignaling,signalingmoleculesarereleasedbyacellandactontargetcellsatadistance.Inanimals,thesignalingmoleculeiscarriedtotargetcellsbythebloodorotherextracellularfluids.Inparacrinesignaling,thesignalingmoleculesarereleasedandaffectonlytargetcellsincloseproximity.Inautocrinesignaling,thecellthatreleasesthesignalingmoleculeisalsothetargetcell.Growthhormoneisanexampleofendocrinesignalingbecausethegrowthhormoneissynthesizedinthepituitary,locatedatthebaseofthebrain,andtravelstotheliverviatheblood.1)Secretedsignalmolecules-dependentcommunicationManysignalmoleculesremainboundtothesurfaceofthesignalingcellandinfluenceonlycellsthatcontactit.Suchcontact-dependentsignalingisespeciallyimportantduringdevelopmentandinimmuneresponses.Contact-dependentsignalingduringdevelopmentcansometimesoperateoverrelativelylargedistances,wherethecommunicatingcellsextendlongprocessestomakecontactwithoneanother.2)Contact-dependentcommunication3)GapJunction-dependentcommunicationGapjunctionsarenarrowwater-filledchannelsthatdirectlyconnectthecytoplasmsofadjacentepithelialcells,&someothercelltypes.Thechannelsallowtheexchangeofinorganicionsandothersmallwatersolublemolecules,butnotofmacromoleculessuchasproteinsornucleicacids.Thus,cellsconnectedbygapjunctionscancommunicatewitheachotherdirectly.Inthisway,gapjunctionsprovideforthemostintimatecellcommunication.Receptorproteinsarepresentintargetcells.Bindingofextracellularsignalingmoleculestocell-surfacereceptorstriggersaconformationalchangeinthereceptor,whichinturnleadstointracellularsignal-transductionpathwaysthatultimatelymodulatecellularmetabolism,function,orgeneexpression.Extracellularsignalsareinitiatedbyreceptors(1)synthesisand(2)releaseofthesignalingmoleculebythesignalingcell;(3)transportofthesignaltothetargetcell;(4)bindingofthesignalbyaspecificreceptorproteinleadingtoaconformationalchange;(5)initiationofoneormoreintracellularsignal-transductionpathwaysbytheactivatedreceptor;(6)specificchangesincellularfunction,metabolism,ordevelopment;(7)feedbackregulationusuallyinvolvingdeactivationofthereceptor;(8)rem