Secretory Vesicles Are Preferentially Targeted to Areas of Low Molecular SNARE Density 英文参考文献.docVIP

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Secretory Vesicles Are Preferentially Targeted to Areas of Low Molecular SNARE Density 英文参考文献.doc

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Secretory Vesicles Are Preferentially Targeted to Areas of Low Molecular SNARE Density 英文参考文献

SecretoryVesiclesArePreferentiallyTargetedtoAreasof LowMolecularSNAREDensity LeiYang1,AlisonR.Dun1,KirstyJ.Martin1,ZhenQiu1,AndrewDunn1,GabrielJ.Lord2,WeipingLu1, RoryR.Duncan1.,ColinRickman1*. 1InstituteofBiologicalChemistry,BiophysicsandBioengineering,Heriot-WattUniversity,Edinburgh,UnitedKingdom,2MathematicalandComputerSciences,Heriot- WattUniversity,Edinburgh,UnitedKingdom Abstract Intercellularcommunicationiscommonlymediatedbytheregulatedfusion,orexocytosis,ofvesicleswiththecellsurface. SNARE (soluble N-ethymaleimide sensitive factor attachment protein receptor) proteins are the catalytic core of the secretorymachinery,drivingvesicleandplasmamembranemerger.PlasmamembraneSNAREs(tSNAREs)areproposedto resideindenseclusterscontainingmanymolecules,thusprovidingaconcentratedreservoirtopromotemembranefusion. However,biophysicalexperimentssuggestthatasmallnumberofSNAREsaresufficienttodriveasinglefusionevent.Here weshow,usingmolecularimaging,thatthemajorityoftSNAREmoleculesarespatiallyseparatedfromsecretoryvesicles. Furthermore, the motilities of the individual tSNAREs are constrained in membrane micro-domains, maintaining a non- random molecular distribution and limiting the maximum number of molecules encountered by secretory vesicles. Together our results provide a new model for the molecular mechanism of regulated exocytosis and demonstrate the exquisiteorganizationoftheplasmamembraneatthelevelofindividualmolecularmachines. Citation:YangL,DunAR,MartinKJ,QiuZ,DunnA,etal.(2012)SecretoryVesiclesArePreferentiallyTargetedtoAreasofLowMolecularSNAREDensity.PLoS ONE7(11):e49514.doi:10.1371/journal.pone.0049514 Editor:LudgerJohannes,InstitutCurie,France ReceivedAugust2,2012;AcceptedOctober10,2012;PublishedNovember15,2012 Copyright: ? 2012 Yang etal. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Fundin