Abstract

Skeletal muscle mass reflects a dynamic turnover between net protein synthesis and degradation. In addition, satellite cell inclusion may contribute to increase muscle mass while fiber loss results in a reduction of muscle mass. Since 2010, a few studies looked at the involvement of the newly discovered Hippo pathway in the regulation of muscle mass. In line with its roles in other organs, it has been hypothesized that the Hippo pathway could play a role in different regulatory mechanisms in skeletal muscle as well, namely proliferation and renewal of satellite cells, differentiation, death, and growth of myogenic cells. While the Hippo components have been identified in skeletal muscle, their role in muscle mass regulation has been less investigated and conflicting results have been reported. Indeed, the first studies described both atrophic and hypertrophic roles of the Hippo pathway and its effectors Yap/Taz using different biochemical approaches. Further, investigation is therefore warranted to determine the role of the Hippo pathway in the regulation of skeletal muscle mass. New components of the pathway will probably emerge and unsuspected roles will likely be discovered due to its numerous interactions with different cellular processes. This mini-review aims to summarize the current literature concerning the roles of the Hippo pathway in the regulation of muscle mass and to develop the hypothesis that this pathway could contribute to muscle mass adaptation after exercise.

Highlights

  • Skeletal muscle mass reflects a dynamic turnover between net protein synthesis and degradation

  • Warts (Wts), core components of the Hippo pathway identified in Drosophila, and their homologs in mammals, large tumor suppressor kinases 1 and 2 (Lats1/2), are protein kinases of the nuclear Dbf2-related (NDR) family (Figure 1)

  • Phosphorylation and Degradation When Yes-Associated Protein (Yap) is phosphorylated at S381, and Transcriptional coactivator with PDZ binding motif (Taz) at S311 by Lats1/2, casein kinase 1 (CK1δ/ε) can in turn phosphorylate Yap at S400 and S403 and Taz at S314 (Zhao et al, 2011)

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Summary

INTRODUCTION

Skeletal muscle mass reflects a dynamic turnover between net protein synthesis and degradation. Skeletal muscle mass regulation is the result of coordinated activation/inhibition of numerous signaling pathways. The canonical Hippo pathway is described in mammals but crosstalks and interplays with other signaling pathways as well as its role in organ size regulation are still unclear (Yu et al, 2015). Its involvement in exercise physiology and muscle mass regulation in non-pathological states has been under-investigated up to now (Watt et al, 2015). This mini-review aims to provide a focused highlight on the Hippo pathway organization, regulation, and involvement in skeletal muscle mass regulation in mammals and to develop the hypothesis that this pathway could contribute to muscle mass adaptation after exercise

ORGANIZATION OF THE HIPPO PATHWAY
Yap and Taz Are Phosphorylated and Inhibited by the Hippo Pathway
UPSTREAM REGULATORS OF THE HIPPO PATHWAY
DOWNSTREAM EFFECTORS OF THE HIPPO PATHWAY
INTERPLAY WITH OTHER SIGNALING PATHWAYS
Hippo and Wnt Pathways
Hippo and Organ Size Control
Hippo and Stem Cells
HIPPO PATHWAY AND SKELETAL MUSCLE MASS REGULATION
Role of the Hippo Pathway during Myogenesis
Role of the Hippo Pathway in Mouse Skeletal Muscle
PERSPECTIVES AND CONCLUSION
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