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

TY - JOUR

T1 - Fine-Tuning of Piezo1 Expression and Activity Ensures Efficient Myoblast Fusion during Skeletal Myogenesis

AU - Ortuste Quiroga, Huascar Pedro

AU - Ganassi, Massimo

AU - Yokoyama, Shingo

AU - Nakamura, Kodai

AU - Yamashita, Tomohiro

AU - Raimbach, Daniel

AU - Hagiwara, Arisa

AU - Harrington, Oscar

AU - Breach-Teji, Jodie

AU - Asakura, Atsushi

AU - Suzuki, Yoshiro

AU - Tominaga, Makoto

AU - Zammit, Peter S.

AU - Goto, Katsumasa

N1 - Funding Information: This work was supported by KAKENHI (JP17K01762, K.G.; JP18H03160, K.G.; JP19K22825, K.G.; 19KK0254. K.G.) from the Japan Society for the Promotion of Science, the Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan, and Graduate School of Health Sciences, Toyohashi SOZO University (K.G.), and NIH R21 (AR0708400) and Regenerative Medicine Minnesota (RMM) 092319 TR010 (A.A.). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/2/1

Y1 - 2022/2/1

N2 - 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.

AB - 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.

KW - Ca channel

KW - Fam38A

KW - Growth

KW - Mechanosensation

KW - Myoblast fusion

KW - Myogenesis

KW - Piezo1

KW - Satellite cells

KW - Skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=85123305626&partnerID=8YFLogxK

U2 - 10.3390/cells11030393

DO - 10.3390/cells11030393

M3 - Article

AN - SCOPUS:85123305626

SN - 2073-4409

VL - 11

JO - Cells

JF - Cells

IS - 3

M1 - 393

ER -