MST1, a Key Player, in Enhancing Fast Skeletal Muscle Atrophy

Abstract

Skeletal muscle undergoes rapid atrophy upon denervation and the process of denervation-induced skeletal muscle atrophy is complicated. MST1 (mammalian sterile 20-like kinase 1) is identified as a central component of Hippo signaling pathway. In the present study, we identified that MST1 kinase was expressed widely in skeletal muscles and found that it was dramatically up-regulated in fast- but not slow-dominant skeletal muscles immediately upon denervation. The results of our histological and biochemical studies demonstrated that deletion of MST1 significantly attenuated denervation-induced skeletal muscle content loss and decreased expression level of Atrogin-1 and LC-3 genes in mice. Further studies indicated that MST1, but not MST2, remarkably increased FOXO3a phosphorylation level at Ser207 and promoted its nuclear translocation in atrophic fast-dominant muscles. Thus, we, in our knowledge for the first time, demonstrated that MST1 kinase plays an important role in regulation of denervation-induced skeletal muscle apotrophy, namely, the upregulated MST1 kinase promoted progression of neurogenic atrophy in fast-dominant skeletal muscles through activation of FOXO3a transcription factors.