Fine-Tuning of Piezo1 Expression and Activity Ensures Efficient Myoblast Fusion during Skeletal Myogenesis

Cells

Daniel Raimbach¹  Oscar Harrington¹  Jodie Breach-Teji¹  Tomohiro Yamashita²  Kodai Nakamura²  Katsumasa Goto²  Arisa Hagiwara²  Huascar Pedro Ortuste Quiroga²  Yoshiro Suzuki³  Makoto Tominaga³  Shingo Yokoyama⁴  Atsushi Asakura⁵  Massimo Ganassi⁶  Peter S. Zammit⁶ 

[1] Centre of Human and Aerospace Physiological Sciences, King’s College London, London SE1 1UL, UK;Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Aichi, Toyohashi 440-0016, Japan;Division of Cell Signalling, National Institute for Physiological Sciences, Aichi, Okazaki 444-0864, Japan;Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University, Aichi, Toyohashi 440-0016, Japan;Paul & Sheila Wellstone Muscular Dystrophy Center, Department of Neurology, Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA;Randall Centre for Cell and Molecular Biophysics, King’s College London, London SE1 1UL, UK;

关键词: skeletal muscle;    satellite cells;    mechanosensation;    Piezo1;    Ca²⁺ channel;    myoblast fusion;   

DOI  :  10.3390/cells11030393

来源: DOAJ

【 摘 要 】

Mechanical stimuli, such as stretch and resistance training, are essential in regulating the growth and functioning of skeletal muscles. However, the molecular mechanisms involved in sensing mechanical stress during muscle formation remain unclear. Here, we investigated the role of the mechanosensitive ion channel Piezo1 during myogenic progression of both fast and slow muscle satellite cells. We found that Piezo1 level increases during myogenic differentiation and direct manipulation of Piezo1 in muscle stem cells alters the myogenic progression. Indeed, Piezo1 knockdown suppresses myoblast fusion, leading to smaller myotubes. Such an event is accompanied by significant downregulation of the fusogenic protein Myomaker. In parallel, while Piezo1 knockdown also lowers Ca²⁺ influx in response to stretch, Piezo1 activation increases Ca²⁺ influx in response to stretch and enhances myoblasts fusion. These findings may help understand molecular defects present in some muscle diseases. Our study shows that Piezo1 is essential for terminal muscle differentiation acting on myoblast fusion, suggesting that Piezo1 deregulation may have implications in muscle aging and degenerative diseases, including muscular dystrophies and neuromuscular disorders.

【 授权许可】

Unknown