Ataxin-3 plays a role in mouse myogenic differentiation through regulation of integrin subunit levels.
During myogenesis several transcription factors and regulators of protein synthesis and assembly are rapidly degraded by the ubiquitin-proteasome system (UPS). Given the potential role of the deubiquitinating enzyme (DUB) ataxin-3 in the UPS, and the high expression of the murine ataxin-3 homolog in muscle during embryogenesis, we sought to define ... its role in muscle differentiation.Using immunofluorescence analysis, we found murine ataxin-3 (mATX3) to be highly expressed in the differentiated myotome of E9.5 mouse embryos. C2C12 myoblasts depleted of mATX3 by RNA interference exhibited a round morphology, cell misalignment, and a delay in differentiation following myogenesis induction. Interestingly, these cells showed a down-regulation of alpha5 and alpha7 integrin subunit levels both by immunoblotting and immunofluorescence. Mouse ATX3 was found to interact with alpha5 integrin subunit and to stabilize this protein by repressing its degradation through the UPS. Proteomic analysis of mATX3-depleted C2C12 cells revealed alteration of the levels of several proteins related to integrin signaling.Ataxin-3 is important for myogenesis through regulation of integrin subunit levels.
Mesh Terms:
Animals, Antigens, CD, Cell Differentiation, Cell Line, Embryo, Mammalian, Female, Fluorescent Antibody Technique, Immunoblotting, Immunoprecipitation, Integrin alpha Chains, Integrin alpha5, Isoelectric Focusing, Mice, Mice, Inbred C57BL, Muscle Development, Myoblasts, Nuclear Proteins, Pregnancy, Protein Binding, Proteomics, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Spectrometry, Mass, Electrospray Ionization, Tandem Mass Spectrometry, Transcription Factors
Animals, Antigens, CD, Cell Differentiation, Cell Line, Embryo, Mammalian, Female, Fluorescent Antibody Technique, Immunoblotting, Immunoprecipitation, Integrin alpha Chains, Integrin alpha5, Isoelectric Focusing, Mice, Mice, Inbred C57BL, Muscle Development, Myoblasts, Nuclear Proteins, Pregnancy, Protein Binding, Proteomics, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Spectrometry, Mass, Electrospray Ionization, Tandem Mass Spectrometry, Transcription Factors
PLoS ONE
Date: Jul. 30, 2010
PubMed ID: 20668528
View in: Pubmed Google Scholar
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