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Mechanosensitive Ion Channel Piezo1 Regulates Myocyte Fusion during Skeletal Myogenesis

View ORCID ProfileHuascar Pedro Ortuste Quiroga, Shingo Yokoyama, View ORCID ProfileMassimo Ganassi, Kodai Nakamura, Tomohiro Yamashita, Daniel Raimbach, Arisa Hagiwara, View ORCID ProfileAtsushi Asakura, Yoshiro Suzuki, View ORCID ProfileMakoto Tominaga, View ORCID ProfilePeter S. Zammit, View ORCID ProfileKatsumasa Goto
doi: https://doi.org/10.1101/2020.09.27.315242
Huascar Pedro Ortuste Quiroga
1Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University
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Shingo Yokoyama
2Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University
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Massimo Ganassi
3Randall Centre for Cell and Molecular Biophysics, King’s College London, London, SE1 1UL, UK
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Kodai Nakamura
1Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University
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Tomohiro Yamashita
1Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University
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Daniel Raimbach
4Centre of Human and Aerospace Physiological Sciences, King’s College London, London, SE1 1UL, UK
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Arisa Hagiwara
1Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University
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Atsushi Asakura
5Stem Cell Institute, Paul & Sheila Wellstone Muscular Dystrophy Center, Department of Neurology, University of Minnesota Medical School
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Yoshiro Suzuki
6Division of Cell Signalling, National Institute for Physiological Sciences
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Makoto Tominaga
6Division of Cell Signalling, National Institute for Physiological Sciences
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Peter S. Zammit
3Randall Centre for Cell and Molecular Biophysics, King’s College London, London, SE1 1UL, UK
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Katsumasa Goto
1Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University
2Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University
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  • For correspondence: gotok@sepia.ocn.ne.jp
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Abstract

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 remain unclear. Here, the purpose of this study was to investigate the role of the mechanosensitive ion channel Piezo1 during myogenic progression. Muscle satellite cell-derived myoblasts and myotubes were modified with stretch, siRNA knockdown and agonist-induced activation of Piezo1. Direct manipulation of Piezo1 modulates terminal myogenic progression. Piezo1 knockdown suppressed myoblast fusion during myotube formation and maturation. This was accompanied by downregulation of the fusogenic protein Myomaker. Piezo1 knockdown also lowered Ca2+ influx in response to stretch. Conversely Piezo1 activation stimulated fusion and increased Ca2+ influx in response to stretch. These evidences indicate that Piezo1 is essential for myotube formation and maturation, which may have implications for msucular dystrophy prevention through its role as a mechanosensitive Ca2+ channel.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Figure 3 updated to include correct images References updated to improve readability Methodology updated to better clarify image quantification

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 22, 2020.
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Mechanosensitive Ion Channel Piezo1 Regulates Myocyte Fusion during Skeletal Myogenesis
Huascar Pedro Ortuste Quiroga, Shingo Yokoyama, Massimo Ganassi, Kodai Nakamura, Tomohiro Yamashita, Daniel Raimbach, Arisa Hagiwara, Atsushi Asakura, Yoshiro Suzuki, Makoto Tominaga, Peter S. Zammit, Katsumasa Goto
bioRxiv 2020.09.27.315242; doi: https://doi.org/10.1101/2020.09.27.315242
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Mechanosensitive Ion Channel Piezo1 Regulates Myocyte Fusion during Skeletal Myogenesis
Huascar Pedro Ortuste Quiroga, Shingo Yokoyama, Massimo Ganassi, Kodai Nakamura, Tomohiro Yamashita, Daniel Raimbach, Arisa Hagiwara, Atsushi Asakura, Yoshiro Suzuki, Makoto Tominaga, Peter S. Zammit, Katsumasa Goto
bioRxiv 2020.09.27.315242; doi: https://doi.org/10.1101/2020.09.27.315242

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