Fanzani Alessandro, Stoppani Elena, Gualandi Laura, Giuliani Roberta, Galbiati Ferruccio, Rossi Stefania, Fra Anna, Preti Augusto, Marchesini Sergio
Department of Biomedical Sciences and Biotechnology, Unit of Biochemistry, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
FEBS Lett. 2007 Oct 30;581(26):5099-104. doi: 10.1016/j.febslet.2007.09.055. Epub 2007 Oct 4.
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 DeltaTFT, 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 DeltaTFT 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.
小窝蛋白-3（Cav-3）是肌纤维小窝中存在的主要支架蛋白。我们分别用导致1C型肢带型肌营养不良的Cav-3显性负性形式P104L或DeltaTFT转染C2C12成肌细胞。这两种形式在C2C12细胞分化过程中均引发Cav-3缺失。P104L突变通过受损的AKT信号传导减少肌纤维形成，同时伴有E3泛素连接酶Atrogin的显著表达。另一方面，DeltaTFT突变通过延长的AKT激活引发肥大性肌管，但与卵泡抑素水平升高和白细胞介素4表达增加无关。这些数据表明，同一营养不良相关基因内的不同突变可能通过不同机制导致肌肉变性。
