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Open Access Research article

MST1, a key player, in enhancing fast skeletal muscle atrophy

Bin Wei1, Wen Dui2, Dong Liu2, Yan Xing1, Zengqiang Yuan2* and Guangju Ji1*

Author affiliations

1 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Datun Road 15, Beijing 100101, China

2 State Key Laboratory of Brain and Cognitive sciences, Institute of Biophysics, Chinese Academy of Sciences, Datun Road 15, Beijing 100101, China

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Citation and License

BMC Biology 2013, 11:12  doi:10.1186/1741-7007-11-12

Published: 1 February 2013

Abstract

Background

Skeletal muscle undergoes rapid atrophy upon denervation and the underlying mechanisms are complicated. FOXO3a has been implicated as a major mediator of muscle atrophy, but how its subcellular location and activity is controlled during the pathogenesis of muscle atrophy remains largely unknown. MST1 (

    M
ammalian
    St
erile 20-like kinase
    1
) is identified as a central component of the Hippo signaling pathway. MST1 has been shown to mediate phosphorylation of FOXO3a at Ser207. Whether this MST1-FOXO signaling cascade exerts any functional consequence on cellular homeostasis remains to be investigated.

Result

We identified that MST1 kinase was expressed widely in skeletal muscles and was dramatically up-regulated in fast- but not slow-dominant skeletal muscles immediately following denervation. The results of our histological and biochemical studies demonstrated that deletion of MST1 significantly attenuated denervation-induced skeletal muscle wasting and decreased expression of Atrogin-1 and LC3 genes in fast-dominant skeletal muscles from three- to five-month-old adult 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.

Conclusions

We have established that MST1 kinase plays an important role in regulating denervation-induced skeletal muscle atrophy. During the early stage of muscle atrophy, the up-regulated MST1 kinase promoted progression of neurogenic atrophy in fast-dominant skeletal muscles through activation of FOXO3a transcription factors.

Keywords:
MST1; muscle atrophy; FOXO3a