A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and Smoothened 英文参考文献.docVIP

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A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and Smoothened 英文参考文献.doc

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A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and Smoothened 英文参考文献

ANovelProteinLZTFL1RegulatesCiliaryTraffickingof theBBSomeandSmoothened SeongjinSeo1,2¤,QihongZhang1,2,KevinBugge1,2,DavidK.Breslow3,CharlesC.Searby1,2,MaxenceV. Nachury3,ValC.Sheffield1,2* 1DepartmentofPediatrics,UniversityofIowaCollegeofMedicine,IowaCity,Iowa,UnitedStatesofAmerica,2HowardHughesMedicalInstitute,ChevyChase,Maryland, UnitedStatesofAmerica,3DepartmentofMolecularandCellularPhysiology,StanfordUniversitySchoolofMedicine,Stanford,California,UnitedStatesofAmerica Abstract Many signaling proteins including G protein-coupled receptors localize to primary cilia, regulating cellular processes including differentiation, proliferation, organogenesis, and tumorigenesis. Bardet-Biedl Syndrome (BBS) proteins are involvedinmaintainingciliaryfunctionbymediatingproteintraffickingtothecilia.However,themechanismsgoverning ciliarytraffickingbyBBSproteinsarenotwellunderstood.Here,weshowthatanovelprotein,Leucine-zippertranscription factor-like1(LZTFL1),interactswithaBBSproteincomplexknownastheBBSomeandregulatesciliarytraffickingofthis complex.WealsoshowthatallBBSomesubunitsandBBS3(alsoknownasARL6)arerequiredforBBSomeciliaryentryand thatreductionofLZTFL1restoresBBSometraffickingtociliainBBS3andBBS5depletedcells.Finally,wefoundthatBBS proteins and LZTFL1 regulate ciliary trafficking of hedgehog signal transducer, Smoothened. Our findings suggest that LZTFL1isanimportantregulatorofBBSomeciliarytraffickingandhedgehogsignaling. Citation:SeoS,ZhangQ,BuggeK,BreslowDK,SearbyCC,etal.(2011)ANovelProteinLZTFL1RegulatesCiliaryTraffickingoftheBBSomeandSmoothened.PLoS Genet7(11):e1002358.doi:10.1371/journal.pgen.1002358 Editor:GregoryS.Barsh,StanfordUniversitySchoolofMedicine,UnitedStatesofAmerica ReceivedJune21,2011;AcceptedSeptember11,2011;PublishedNovember3,2011 Copyright:?2011Seoetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredi