Fine-Tuning of Piezo1 Expression and Activity Ensures Efficient Myoblast Fusion during Skeletal Myogenesis
Huascar Pedro Ortuste Quiroga,
Massimo Ganassi,
Shingo Yokoyama,
Kodai Nakamura,
Tomohiro Yamashita,
Daniel Raimbach,
Arisa Hagiwara,
Oscar Harrington,
Jodie Breach-Teji,
Atsushi Asakura,
Yoshiro Suzuki,
Makoto Tominaga,
Peter S. Zammit,
Katsumasa Goto
Affiliations
Huascar Pedro Ortuste Quiroga
Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Aichi, Toyohashi 440-0016, Japan
Massimo Ganassi
Randall Centre for Cell and Molecular Biophysics, King’s College London, London SE1 1UL, UK
Shingo Yokoyama
Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University, Aichi, Toyohashi 440-0016, Japan
Kodai Nakamura
Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Aichi, Toyohashi 440-0016, Japan
Tomohiro Yamashita
Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Aichi, Toyohashi 440-0016, Japan
Daniel Raimbach
Centre of Human and Aerospace Physiological Sciences, King’s College London, London SE1 1UL, UK
Arisa Hagiwara
Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Aichi, Toyohashi 440-0016, Japan
Oscar Harrington
Centre of Human and Aerospace Physiological Sciences, King’s College London, London SE1 1UL, UK
Jodie Breach-Teji
Centre of Human and Aerospace Physiological Sciences, King’s College London, London SE1 1UL, UK
Atsushi Asakura
Paul & Sheila Wellstone Muscular Dystrophy Center, Department of Neurology, Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA
Yoshiro Suzuki
Division of Cell Signalling, National Institute for Physiological Sciences, Aichi, Okazaki 444-0864, Japan
Makoto Tominaga
Division of Cell Signalling, National Institute for Physiological Sciences, Aichi, Okazaki 444-0864, Japan
Peter S. Zammit
Randall Centre for Cell and Molecular Biophysics, King’s College London, London SE1 1UL, UK
Katsumasa Goto
Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Aichi, Toyohashi 440-0016, Japan
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.
