Ataxin-3 Plays a Role in Mouse Myogenic Differentiation through Regulation of Integrin Subunit LevelsReport as inadecuate




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Background

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.

Methodology-Principal Findings

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 α5 and α7 integrin subunit levels both by immunoblotting and immunofluorescence. Mouse ATX3 was found to interact with α5 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.

Conclusions

Ataxin-3 is important for myogenesis through regulation of integrin subunit levels.



Author: Maria do Carmo Costa, Fernanda Bajanca, Ana-João Rodrigues, Ricardo J. Tomé, Garry Corthals, Sandra Macedo-Ribeiro, Henry L. Pa

Source: http://plos.srce.hr/



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