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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number393
JournalCells
Volume11
Issue number3
Early online date24 Jan 2022
DOIs
Publication statusPublished - 1 Feb 2022

Keywords

  • Ca channel
  • Fam38A
  • Growth
  • Mechanosensation
  • Myoblast fusion
  • Myogenesis
  • Piezo1
  • Satellite cells
  • Skeletal muscle

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