PT  - JOURNAL ARTICLE
AU  - Huascar Pedro Ortuste Quiroga
AU  - Massimo Ganassi
AU  - Shingo Yokoyama
AU  - Kodai Nakamura
AU  - Tomohiro Yamashita
AU  - Daniel Raimbach
AU  - Arisa Hagiwara
AU  - Oscar Harrington
AU  - Jodie Breach-Teji
AU  - Atsushi Asakura
AU  - Yoshiro Suzuki
AU  - Makoto Tominaga
AU  - Peter S. Zammit
AU  - Katsumasa Goto
TI  - Fine tuning of Piezo1 Expression and Activity Ensures Efficient Myoblast Fusion during Skeletal Myogenesis
AID  - 10.1101/2020.09.27.315242
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2020.09.27.315242
4099  - http://biorxiv.org/content/early/2021/11/27/2020.09.27.315242.short
4100  - http://biorxiv.org/content/early/2021/11/27/2020.09.27.315242.full
AB  - Mechanical stimuli such as stretch and resistance training are essential to regulate growth and function of skeletal muscle. However, the molecular mechanisms involved in sensing mechanical stress during muscle formation remain unclear. Here, we investigate the role of the mechano-sensitive ion channel Piezo1 during myogenic progression. Direct manipulation of Piezo1 in muscle stem cells alters their myogenic progression. Indeed, Piezo1 knockdown suppresses myoblast fusion leading to smaller myotubes. Such 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. We believe these findings may help understand molecular defects present in some muscle diseases. Altogether 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.Competing Interest StatementThe authors have declared no competing interest.