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

Authors :
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
Source :
Cells, Vol 11, Iss 3, p 393 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

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.

Details

Language :
English
ISSN :
20734409
Volume :
11
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.7d772610dfa4790ac37f073dd433061
Document Type :
article
Full Text :
https://doi.org/10.3390/cells11030393