Coordinated maintenance of the size control of muscle cells by AMP‐activated protein kinase

Abstract

Skeletal muscle mass is regulated by signaling pathways that govern protein synthesis and cell proliferation, the mammalian target of rapamycin (mTOR) playing a key role in these processes. Recent studies have suggested the crucial role of AMP‐activated protein kinase (AMPK) in the inhibition of protein synthesis and cell growth. Here, we address the role of AMPK in the regulation of muscle cell size in vitro and in vivo . The size of myotubes lacking both AMPKα1 and α2 catalytic subunits was 1.5‐fold higher than for controls. A marked increase in p70S6K Thr389 and rpS6 Ser235/236 phosphorylation was observed concomitant with an up‐regulation of protein synthesis rate. Inhibition of mTOR pathway by AMPK activators (AICAR, metformin, A‐769662) was blunted and was correlated with altered raptor phosphorylation. However, treatment with rapamycin prevented both p70S6K phosphorylation and cell hypertrophy. Moreover, in skeletal muscle‐specific deficient AMPKα1/α2 KO mice, soleus muscle showed a higher mass with myofibers of larger size and was correlated with enhanced p70S6K and rpS6 phosphorylation. Our results demonstrate the cross talk between AMPK and mTOR/p70S6K pathways in muscle cell size control. ANR‐06‐PHYSIO‐026