Phenotypic behavior of C2C12 myoblasts upon expression of the dystrophy-related caveolin-3 P104L and TFT mutants

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• 作者：Aless ; ro Fanzani ; Elena Stoppani ; Laura Gual ; i ; Roberta Giuliani ; Ferruccio Galbiati ; Stefania Rossi ; Anna Fra ; Augusto Preti ; Sergio Marchesini
• 关键词：Caveolin 3 ; Dystrophy ; AKT ; Follistatin ; NFATC2 ; IL-4 ; Murf-1 ; Atrogin
• 刊名：FEBS Letters
• 出版年：2007
• 出版时间：30 October 2007
• 年：2007
• 卷：581
• 期：26
• 页码：5099-5104
• 全文大小：616 K

文摘

Caveolin-3 (Cav-3) is the main scaffolding protein present in myofiber caveolae. We transfected C2C12 myoblasts with dominant negative forms of Cav-3, P104L or ΔTFT, respectively, which cause the limb-girdle muscular dystrophy 1-C. Both these forms triggered Cav-3 loss during C2C12 cell differentiation. The P104L mutation reduced myofiber formation by impaired AKT signalling, accompanied by dramatic expression of the E3 ubiquitin ligase Atrogin. On the other hand, the ΔTFT mutation triggered hypertrophic myotubes sustained by prolonged AKT activation, but independent of increased levels of follistatin and interleukin 4 expression. These data suggest that separated mutations within the same dystrophy-related gene may cause muscle degeneration through different mechanisms.