An Initial Step of GAS-Containing Autophagosome-Like Vacuoles Formation Requires Rab7 英文参考文献.docVIP

An Initial Step of GAS-Containing Autophagosome-Like Vacuoles Formation Requires Rab7 英文参考文献.doc

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An Initial Step of GAS-Containing Autophagosome-Like Vacuoles Formation Requires Rab7 英文参考文献

AnInitialStepofGAS-ContainingAutophagosome-Like VacuolesFormationRequiresRab7 HitomiYamaguchi1,2.,IchiroNakagawa3,4.,AkitsuguYamamoto5,AtsuoAmano6,7,TakeshiNoda2, TamotsuYoshimori2,7 * 1StructuralBiologyCenter,NationalInstituteofGenetics/SOKENDAI,Mishima-Shizuoka,Japan,2DepartmentofCellRegulation,ResearchInstituteforMicrobialDiseases, OsakaUniversity,Suita-Osaka,Japan,3SectionofBacterialPathogenesis,TokyoMedicalandDentalUniversity,Bunkyo-ku,Tokyo,Japan,4PRESTO,JapanScienceand TechnologyAgency,Kawaguchi-Saitama, Japan, 5Department of CellBiology, FacultyofBio-Science,Nagahama Institute ofBio-ScienceandTechnology,Nagahama- Shiga,Japan,6DepartmentofOralFrontierBiology,OsakaUniversityGraduateSchoolofDentistry,Suita-Osaka,Japan,7CREST,JapanScienceandTechnologyAgency, Kawaguchi-Saitama,Japan Abstract GroupAstreptococcus(GAS;Streptococcuspyogenes)isacommonpathogenthatinvadesnon-phagocytichumancellsvia endocytosis.Oncetakenupbycells,itescapesfromtheendocyticpathwaytothecytoplasm,buthereitiscontainedwithin amembrane-boundstructuretermedGAS-containingautophagosome-likevacuoles(GcAVs).Theautophagosomemarker GFP-LC3associateswithGcAVs,andothercomponentsoftheautophagosomalpathwayareinvolvedinGcAVformation. However, the mechanistic relationship between GcAV and canonical autophagy is largely unknown. Here, we morphologicallyanalyzedGcAVformationindetail.Initially,asmall,GFP-LC3-positiveGcAVsequesterseachstreptococcal chain,andthesethencoalesceintoasingle,largeGcAV.Expressionofadominant-negativeformofRab7orRNAi-mediated knockdownofRab7preventedtheinitialformationofsmallGcAVstructures.Ourresultsdemonstratethatmechanismsof GcAVformationincludesnotonlythecommonmachineryofautophagy,butalsoRab7asanadditionalcomponent,which isdispensableincanonicalautophagosomeformation. Citation:YamaguchiH,NakagawaI,YamamotoA,AmanoA,NodaT,etal.(2009)AnInitialStepofGAS-ContainingAutophagosome-LikeVacuolesFormation RequiresRab7.PLoSPathog5(11):e1000670.doi:10.1371/journal.ppat.1000670 Editor:VojoDer

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