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1、VesicleFormationatthePlasmaMembraneandTrans-GolgiNetwork:TheSamebutDifferentM.A.McNiven,etal.,Science313,1591(2006)DepartmentofBiochemistryandMolecularBiologyandtheMilesandShirleyFitermanCenterforDigestiveDiseases,MayoClinicCollegeofMedicine,RochesterLiangfangZ
2、hao,YanqingLin&ZhilingYaoLifeScienceCollege,CNU2007.10.30AbbreviationsPM:PlasmaMembraneTGN:Trans-GolgiNetworkCCV:Clathrin-CoatedVesicleAPs:AdaptorProteinsEGF:EpidermalGrowthReceptorGGAs:Golgi-localized,γ-earcontaining,AdenosinediphosphateRibosylationFactor(ARF)
3、PIP2:PhosphatidylInositol4,5-bisPhosphatePI4P:PhosphatidylInositol4-monoPhosphateUIMs:UbiquitinInteractingMotifsOverview:yin&yangrelationshipSorting,packaging,vesiculation,transportofmembraneandproteincargoactiveexchangeofmembranes&proteincargo;highlyconservedm
4、echanismsinvesicleformation&scissionInandoutofthecellMembranecontinuumIndexI.similaritiesandvariationsinsortingmechanismsII.Lipid-membranebinding,bendingandpinchingIII.VesiclescissionI.similaritiesandvariationsinsortingmechanismsSimilaritiesinprotein-sortingmec
5、hanismsatthePMandTGNVariationsofacommonsortingmachine1.Similaritiesinprotein-sortingmechanismsatthePMandTGNKeyfunctions:selectivesequestrationandpackagingofproteincargoCentralscaffold:clathrinanditsassociatedcoatproteinsAPsandmonomericclathrin-associatedsorting
6、proteins“firstline”ofcargo-sequestrationspecificityAP1-4similarorganization,subunits,structure;differentcellularlocalizationpatterns,vesicle-formationprocessesAP:mediateproteinsortingRecognitionofsortingmotifsofthecytosolicdomainsoftransmembraneproteinsThreecla
7、ssesAsn-Pro-X-Tyr:AP-2atthePMwhileinteractwithnon-AP-2Tyr-X-X-Φ:μsubunitofall4APs[Asp-Glu]X-X-X-Leu[Leu-Ile]:AP1-3yetdifferentpreferencesConclusionforPART1Differentaffinitiesbetweenleavingandbeinginternalized2.VariationsofacommonsortingmachineSeverallayersofreg
8、ulationandtargeting:providespecificityDifferentlipids&phosphoinositides;smallGTPases;GGAsLipidsCholesterol,sphingoipids,phosphoinositidesRafts(lipidmicrodomains)mediateclath
