Downregulation of the Hsp90 System Causes Defects in Muscle Cells of Caenorhabditis Elegans 英文参考文献.docVIP

DownregulationoftheHsp90SystemCausesDefectsin MuscleCellsofCaenorhabditisElegans AndreasM.Gaiser.,ChristophJ.O.Kaiser.,VeronikaHaslbeck.,KlausRichter* DepartmentofChemistryandCenterforIntegratedProteinScienceMunich(CIPSM)andTechnischeUniversita¨t Mu¨nchen,Mu¨nchen,Germany Abstract The ATP-dependent molecular chaperone Hsp90 is required for the activation of a variety of client proteins involved in variouscellularprocesses.Despitetheabundanceofknownclientproteins,functionsofHsp90intheorganismalcontext arenotfullyexplored.InCaenorhabditiselegans,Hsp90(DAF-21)hasbeenimplicatedintheregulationofthestress-resistant dauerstate,inchemosensingandingonadformation.InaC.elegansstraincarryingaDAF-21mutationwithalowerATP turnover, we observed motility defects. Similarly, a reduction of DAF-21 levels in wild type nematodes leads to reduced motilityandinductionofthemuscularstressresponse.Furthermore,aggregatesofthemyosinMYO-3arevisibleinmuscle cells,ifDAF-21isdepleted,implyingaroleofHsp90inthemaintenanceofmusclecellfunctionality.Similardefectscanalso beobserveduponknockdownoftheHsp90-cochaperoneUNC-45.InlifenematodesYFP-DAF-21localizestotheI-bandand the M-line of the muscular ultrastructure, but the protein is not stably attached there. The Hsp90-cofactor UNC-45-CFP contrarily can be found in all bands of the nematode muscle ultrastructure and stably associates with the UNC-54 containingA-band.Thus,despitethephysicalinteractionbetweenDAF-21andUNC-45,apparentlythetwoproteinsarenot always localized to the same muscular structures. While UNC-45 can stably bind to myofilaments in the muscular ultrastructure,Hsp90(DAF-21)appearstoparticipateinthemaintenanceofmusclestructuresasatransientlyassociated diffusiblefactor. Citation:GaiserAM,KaiserCJO,HaslbeckV,RichterK(2011)DownregulationoftheHsp90SystemCausesDefectsinMuscleCellsofCaenorhabditisElegans .PLoS ONE6(9):e25485.doi:10.1371/journal.pone.0025485 Editor:EllenA.A.Nollen,UniversityMedicalCenterGroningen,TheNetherlands ReceivedJ