复旦细胞生物学课件07内膜系统、蛋白质分类和膜运输

Chapter7Endomembranesystem,ProteinSortingandmembranetrafficingLearningobjective1.CompartmentalizationinEukaryoticCells;2.ThestructuralandfunctionalrelationshipbetweentheER,Golgicomplexes,lysosomesandplasmamembranesofeukaryoticcells;3.Thepathwaysofproteinstargetingandsorting,anditsmechanisms;4.Thewaysofproteinmodificationsandintracellularsitesaftertheyaresynthesized;5.Typesofvesicletransportandtheirfunctions.1.TheCompartmentalizationinEukaryoticCellsMembranesdividethecytoplasmofeukaryoticcellsintodistinctcompartments.Treecategoriesineukaryoticcells:(1)theendomembranesystem:ER,Golgicomplex,Lys.,secretoryvesicles.(2)thecytosol.(3)mitochondria,chloroplasts,peroxisomes,andthenucleus.Membrane-boundstructures(organelles)arefoundinalleukaryoticcells.Cytosol:Theregionoffluidcontentofthecytoplasmoutsideofthemembranousorganelles.Aqueoussolutionoflargeandsmallmoleculesincludingfilamentsofcytoskeletonwhichactasorganizerforsomeorder.TheCytosolisthesiteofproteinsynthesisanddegradationormodification.Italsoperformsmostofthecell’sintermediarymetabolism.A.CytosolanditsfunctionsB.EndomembraneSystemEndomembraneSystem:ThestructuralandfunctionalrelationshiporganellesincludingER,Golgicomplex,lysosome,endosomes,secretoryvesicles.Membrane-boundstructures(organelles)arefoundinalleukaryoticcells.Intracellularcompartment%oftotalcellvolumeCytosol54Mittchondria22RoughERcisternae9SmoothERcisternaeplusGolgicisternae6Nucleus6Peroxisome1Lysosomes1Endosomes1RelativevolumesoccupiedbythemajorintracellularcompartmentsinLiverCellC.TheDynamicNatureoftheEndomembraneSystemMostorganellesarepartofadynamicsysteminwhichvesiclesmovebetweencompartments.Biosyntheticpathwaysmoveproteins,carbohydratesandlipidswithinthecell.Secretarypathwaysdischargeproteinsfromcells.Endocyticpathwaysmovematerialsintocells.Sortingsignalsarerecognizedbyreceptorsandtargetproteinstospecificsites.D.AfewapproachestothestudyofcytomembranesInsightsgainedfromautoradiography;Insightsgainedfromthebiochemicalanalysisofsubcellularfractions;Insightsgainedfromthestudyofgeneticmutants;Thedynamicactivitiesofendomembranesystemsarehighlyconserveddespitethestructuraldiversityofdifferentcelltypes.DeDuve,A.ClaudeandG.Palade,1974NobelPlrize2.ThestructureandfunctionsofEndoplasmicReticulum(ER)A.FunctionsoftherERProteinssynthesizedonribosomesofrERinclude:secretoryproteins,integralmembraneproteins,solubleproteinsoforganelles.Modificationandprocessingofnewlysynthesizedproteins:glycosylationintherER;N-linked:linkedtotheamidenitrogenofasparagine(ER)O-linked:linkedtothehydroxylgroupserineorthreonineviaGalNac(inGolgi)Theprecursorof14residuesisthesameinplants,animals,andsingle-celledeukaryotesthenremove3glucosesand1mannoseintheERQualitycontrolofnewlysynthesizedproteins---TheroleofN-linkedglycosylationinERproteinfoldingSynthesis0fmembranelipidsMostmembranelipidsaresynthesizedenterelywithintheER.Therearetwoexceptions:(1)sphingomyelinandglycolipids,(beginsinER;completedinGolgi);(2)someoftheuniquelipidsoftheMitandChlmembranes(themself).Themembranesofdifferent0rganelleshavemarkdlydifferentlipidscomposition.Transportbybudding：ER→GC、Ly、PMTransportbyphospholipidexchangeproteins(PEP)：ER→otherorganelles（includingMitandChl）Theroleofphospholipidtranslocatorsinlipidbilayersynthesisphospholipidtranslocators=Scramblase(ABCtransporterFamily)B.FunctionsofthesERSynthesisofsteroidsinendocrinecells.Detoxificationoforganiccompoundsinlivercells.Systemofoxygenases---cytochromep450familyReleaseofglucose6-phosphateinlivercells.SequestrationofCa2+.Ca2+-ATPase3.ThestructureandfunctionsofGolgicomplexA.ThepolarityofGolgicomplexa)CiscisternaeofGolgicomplex:reducedosmiumtetroxide;b)ReactionforenzymemannosidaseII,localizedinthemedial;c)Reactionforenzymenucleosidediphosphatase,localizedinthetranscisternae.RegionaldifferencesinmembranecompositionacrosstheGolgistackB.TheFunctionsofGolgicomplexGlycosylationintheGolgicomplexGolgicomplexplaysakeyroleintheassemblyofthecarbohydratecomponentofglycoproteinsandglycolipids.ThecorecarbohydrateofN-linkedoligosaccharidesisassembledintherER.ModificationstoN-linkedoligosaccharidesarecompletedintheGolgicomplex.O-linkedoligosaccharidestakesplaceinGolgicomplex.StructureoftypicalO-andN-linkedoligosaccharidesCoreRegionWhatisthepurposeofglycosylation?N-linkedglycosylationisprevalentinalleukaryotes,butisabsentfromprokaryotes.Itdoesn’trequireatemplate.ThereisanimportantdifferencebetweentheconstructionofanoligosaccharideandthesynthesisofDNA,RNA,andprotein.Importantfunctions:(1)Onemightsuspectthattheyfunctiontoaidfoldingandthetransportprocess;forexample,carbohydrateasamarkerduringproteinfoldinginERandtheuseofcarbohydrate-bindinglectinsinguidingER-to-Golgitransport.(2)Limittheapproachofothermacromoleculestotheproteinsurface,moreresistanttodigestionbyproteases.(3)Regulatoryrolesinsignalingthroughthecell-surfacereceptorNotch,toallowsthesecellstorespondselectivelytoactivatingstimuli.TheGolginetworksareprocessingandsortingstationswhereproteinsaremodified,segregatedandthenshippedind