Botulinum Neurotoxin D Uses Synaptic Vesicle Protein SV2 and Gangliosides as Receptors 英文参考文献.docVIP

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Botulinum Neurotoxin D Uses Synaptic Vesicle Protein SV2 and Gangliosides as Receptors 英文参考文献.doc

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Botulinum Neurotoxin D Uses Synaptic Vesicle Protein SV2 and Gangliosides as Receptors 英文参考文献

BotulinumNeurotoxinDUsesSynapticVesicleProtein SV2andGangliosidesasReceptors LishengPeng1,WilliamH.Tepp2,EricA.Johnson2,MinDong1* 1Department of Microbiology and Molecular Genetics, Harvard Medical School and Division of Neuroscience, New England Primate Research Center, Southborough, Massachusetts,UnitedStatesofAmerica,2DepartmentofFoodMicrobiologyandToxicology,UniversityofWisconsin,Madison,Wisconsin,UnitedStatesofAmerica Abstract Botulinum neurotoxins (BoNTs) include seven bacterial toxins (BoNT/A-G) that target presynaptic terminals and act as proteasescleavingproteinsrequiredforsynapticvesicleexocytosis.HereweidentifiedsynapticvesicleproteinSV2asthe proteinreceptorforBoNT/D.BoNT/DentersculturedhippocampalneuronsviasynapticvesiclerecyclingandcanbindSV2 inbraindetergentextracts.BoNT/DfailedtobindandenterneuronslackingSV2,whichcanberescuedbyexpressingone ofthethreeSV2isoforms(SV2A/B/C).LocalizationofSV2onplasmamembranesmediatedBoNT/Dbindinginbothneurons andHEK293cells.Furthermore,chimericreceptorscontainingthebindingsitesforBoNT/AandE,twootherBoNTsthatuse SV2asreceptors,failedtomediatetheentryofBoNT/DsuggestingthatBoNT/DbindsSV2viaamechanismdistinctfrom BoNT/AandE.Finally,wedemonstratedthatgangliosidesareessentialforthebindingandentryofBoNT/Dintoneurons andforitstoxicityinvivo,supportingadouble-receptormodelforthistoxin. Citation: Peng L, Tepp WH, Johnson EA, Dong M (2011) Botulinum Neurotoxin D Uses Synaptic Vesicle Protein SV2 and Gangliosides as Receptors. PLoS Pathog7(3):e1002008.doi:10.1371/journal.ppat.1002008 Editor:TheresaKoehler,TheUniversityofTexas-HoustonMedicalSchool,UnitedStatesofAmerica ReceivedOctober6,2010;AcceptedJanuary10,2011;PublishedMarch31,2011 Copyright: ? 2011 Peng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisstudywassupportedbyNationalCenterforRes