Fanzani Alessandro, Musarò Antonio, Stoppani Elena, Giuliani Roberta, Colombo Francesca, Preti Augusto, Marchesini Sergio
Department of Biomedical Sciences and Biotechnology, Unit of Biochemistry, University of Brescia, Italy.
Biochem Biophys Res Commun. 2007 May 25;357(1):314-8. doi: 10.1016/j.bbrc.2007.03.148. Epub 2007 Apr 2.
Caveolin-3 (Cav-3) is a muscle-specific membrane protein crucial for myoblast differentiation, as loss of the protein due to mutations within the gene causes an autosomal dominant form of limb girdle muscular dystrophy 1-c. Here we show that along with p38 activity the PI3-kinase/AKT/mTOR pathway is required for proper Cav-3 up-regulation during muscle differentiation and hypertrophy, as confirmed by the marked increase of Cav-3 expression in hypertrophied C2C12 cells transfected with an activated form of AKT. Accordingly, Cav-3 expression was further increased during hypertrophy of L6C5 myoblasts treated with Arg(8)-vasopressin and in hypertrophic muscles of MLC/mIGF-1 transgenic mice. In contrast, Cav-3 expression was down-regulated in C2C12 myotubes exposed to atrophic stimuli such as starvation or treatment with dexamethasone. This study clearly suggests that Cav-3 expression is causally linked to the maturation of muscle phenotype and it is tightly regulated by hypertrophic and atrophic stimuli.
小窝蛋白3（Cav-3）是一种肌肉特异性膜蛋白，对成肌细胞分化至关重要，因为该基因突变导致的蛋白缺失会引起常染色体显性遗传的1C型肢带型肌营养不良。我们在此表明，与p38活性一样，PI3激酶/AKT/mTOR信号通路在肌肉分化和肥大过程中对于Cav-3的正常上调是必需的，这一点通过转染活化型AKT的肥大C2C12细胞中Cav-3表达的显著增加得到证实。相应地，在用精氨酸加压素处理的L6C5成肌细胞肥大过程以及MLC/mIGF-1转基因小鼠的肥大肌肉中，Cav-3表达进一步增加。相反，在暴露于萎缩刺激（如饥饿或地塞米松处理）的C2C12肌管中，Cav-3表达下调。本研究清楚地表明，Cav-3表达与肌肉表型成熟存在因果联系，并且受到肥大和萎缩刺激的严格调控。
