Ryanodine receptor RyR1-mediated elevation of Ca2+ concentration is required for the late stage of myogenic differentiation and fusion

文献类型： 外文期刊

第一作者： Qiu, Kai

作者： Qiu, Kai;Wang, Yubo;Xu, Doudou;He, Linjuan;Zhang, Xin;Yan, Enfa;Wang, Lu;Yin, Jingdong;Qiu, Kai

作者机构：

关键词： Apoptosis; Ca2+ homeostasis; Endoplasmic reticulum stress; Myoblast fusion; Myogenic differentiation; RyR1 knockout

期刊名称：JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY （ 影响因子：6.175； 五年影响因子：6.853 ）

ISSN： 1674-9782

年卷期： 2022 年 13 卷 1 期

页码：

收录情况： SCI

摘要： Background Cytosolic Ca2+ plays vital roles in myogenesis and muscle development. As a major Ca2+ release channel of endoplasmic reticulum (ER), ryanodine receptor 1 (RyR1) key mutations are main causes of severe congenital myopathies. The role of RyR1 in myogenic differentiation has attracted intense research interest but remains unclear. Results In the present study, both RyR1-knockdown myoblasts and CRISPR/Cas9-based RyR1-knockout myoblasts were employed to explore the role of RyR1 in myogenic differentiation, myotube formation as well as the potential mechanism of RyR1-related myopathies. We observed that RyR1 expression was dramatically increased during the late stage of myogenic differentiation, accompanied by significantly elevated cytoplasmic Ca2+ concentration. Inhibition of RyR1 by siRNA-mediated knockdown or chemical inhibitor, dantrolene, significantly reduced cytosolic Ca2+ and blocked multinucleated myotube formation. The elevation of cytoplasmic Ca2+ concentration can effectively relieve myogenic differentiation stagnation by RyR1 inhibition, demonstrating that RyR1 modulates myogenic differentiation via regulation of Ca2+ release channel. However, RyR1-knockout-induced Ca2+ leakage led to the severe ER stress and excessive unfolded protein response, and drove myoblasts into apoptosis. Conclusions Therefore, we concluded that Ca2+ release mediated by dramatic increase in RyR1 expression is required for the late stage of myogenic differentiation and fusion. This study contributes to a novel understanding of the role of RyR1 in myogenic differentiation and related congenital myopathies, and provides a potential target for regulation of muscle characteristics and meat quality.

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