Stabilin-2 modulates the efficiency of myoblast fusion during myogenic differentiation and muscle regeneration.

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2016

Nat Commun. 2016 Mar 14;7:10871. doi: 10.1038/ncomms10871.

Stabilin-2 modulates the efficiency of myoblast fusion during myogenic differentiation and muscle regeneration

SY Park;Y Yun;JS Lim;MJ Kim;SY Kim;JE Kim;IS Kim

Dongguk University, Gyeongju 780-714, Republic of Korea. Kyungpook National University, Daegu 700-422, Republic of Korea. Asan Medical Center, Seoul 138-736, Republic of Korea. Korea Institute Science and Technology, Seoul 136-791, Republic of Korea. Korea University, Seoul 136-701, Republic of Korea.

Service type: Knockout mice

Abstract

Myoblast fusion is essential for the formation of skeletal muscle myofibres. Studies have shown that phosphatidylserine is necessary for myoblast fusion, but the underlying mechanism is not known. Here we show that the phosphatidylserine receptor stabilin-2 acts as a membrane protein for myoblast fusion during myogenic differentiation and muscle regeneration. Stabilin-2 expression is induced during myogenic differentiation, and is regulated by calcineurin/NFAT signalling in myoblasts. Forced expression of stabilin-2 in myoblasts is associated with increased myotube formation, whereas deficiency of stabilin-2 results in the formation of small, thin myotubes. Stab2-deficient mice have myofibres with small cross-sectional area and few myonuclei and impaired muscle regeneration after injury. Importantly, myoblasts lacking stabilin-2 have reduced phosphatidylserine-dependent fusion. Collectively, our results show that stabilin-2 contributes to phosphatidylserine-dependent myoblast fusion and provide new insights into the molecular mechanism by which phosphatidylserine mediates myoblast fusion during muscle growth and regeneration.

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