Ataxin-3 Plays a Role in Mouse Myogenic Differentiation through Regulation of Integrin Subunit Levels 英文参考文献.docVIP

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Ataxin-3 Plays a Role in Mouse Myogenic Differentiation through Regulation of Integrin Subunit Levels 英文参考文献.doc

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Ataxin-3 Plays a Role in Mouse Myogenic Differentiation through Regulation of Integrin Subunit Levels 英文参考文献

Ataxin-3PlaysaRoleinMouseMyogenicDifferentiation throughRegulationofIntegrinSubunitLevels MariadoCarmoCosta1,2,FernandaBajanca1¤,Ana-Joa?oRodrigues1,RicardoJ.Tome′3,GarryCorthals4, SandraMacedo-Ribeiro3,HenryL.Paulson2,ElsaLogarinho1,3,Patr?′ciaMaciel1* 1LifeandHealthSciencesResearchInstitute(ICVS),SchoolofHealthSciences,UniversityofMinho,Braga,Portugal,2DepartmentofNeurology,UniversityofMichigan, Ann Arbor, Michigan, United States of America, 3Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal, 4Turku Center for Biotechnology,Turku,Finland Abstract Background:Duringmyogenesisseveraltranscriptionfactorsandregulatorsofproteinsynthesisandassemblyarerapidly degradedbytheubiquitin-proteasomesystem(UPS).Giventhepotentialroleofthedeubiquitinatingenzyme(DUB)ataxin- 3intheUPS,andthehighexpressionofthemurineataxin-3homologinmuscleduringembryogenesis,wesoughttodefine itsroleinmuscledifferentiation. Methodology/Principal Findings: Using immunofluorescence analysis, we found murine ataxin-3 (mATX3) to be highly expressedinthedifferentiatedmyotomeofE9.5mouseembryos.C2C12myoblastsdepletedofmATX3byRNAinterference exhibited a round morphology, cell misalignment, and a delay in differentiation following myogenesis induction. Interestingly, these cells showed a down-regulation of a5 and a7 integrin subunit levels both by immunoblotting and immunofluorescence.MouseATX3wasfoundtointeractwitha5integrinsubunitandtostabilizethisproteinbyrepressing its degradation through the UPS. Proteomic analysis of mATX3-depleted C2C12 cells revealed alteration of the levels of severalproteinsrelatedtointegrinsignaling. Conclusions:Ataxin-3isimportantformyogenesisthroughregulationofintegrinsubunitlevels. Citation:CostaMdC,BajancaF,RodriguesA-J,Tome′ RJ,CorthalsG,etal.(2010)Ataxin-3PlaysaRoleinMouseMyogenicDifferentiationthroughRegulationof IntegrinSubunitLevels.PLoSONE5(7):e11728.doi:10.1371/journal.pone.0011728 Editor:ChristophWinkler,NationalUniversityofSingap