ataxin-3 plays a role in mouse myogenic differentiation through regulation of integrin subunit levelsataxin-3扮演了一个角色在小鼠肌原性的分化是通过整合素亚单位的监管水平.pdfVIP

Ataxin-3 Plays a Role in Mouse Myogenic Differentiation through Regulation of Integrin Subunit Levels 1,2 1¤ ˜ 1 ´ 3 4 Maria do Carmo Costa , Fernanda Bajanca , Ana-Joao Rodrigues , Ricardo J. Tome , Garry Corthals , 3 2 1,3 ´ 1 Sandra Macedo-Ribeiro , Henry L. Paulson , Elsa Logarinho , Patrıcia Maciel * 1 Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal, 2 Department of Neurology, University of Michigan, Ann Arbor, Michigan, United States of America, 3 Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal, 4 Turku Center for Biotechnology, Turku, Finland Abstract 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-