Mg <sup>2+</sup> influx mediated by TRPM7 triggers the initiation of muscle stem cell activation

DOI Web Site 65 References Open Access
  • Kotaro Hirano
    School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
  • Chika Nakabayashi
    School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
  • Mao Sasaki
    School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
  • Miki Suzuki
    School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
  • Yuta Aoyagi
    School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
  • Kaori Tanaka
    Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
  • Akira Murakami
    School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
  • Masaki Tsuchiya
    School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
  • Eiji Umemoto
    School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
  • Shuji Takabayashi
    Institute of Photonics Medicine, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
  • Yasuo Kitajima
    Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
  • Yusuke Ono
    Department of Muscle Development and Regeneration, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.
  • Takehisa Matsukawa
    Faculty of Pharmacy, Laboratory of Hygienic Chemistry, Juntendo University, Chiba 279-0013, Japan.
  • Masayuki Matsushita
    Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0213, Japan.
  • Yasuyuki Ohkawa
    Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
  • Yasuo Mori
    Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
  • Yuji Hara
    School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.

Bibliographic Information

Published
2025-04-04
Resource Type
journal article
DOI
  • 10.1126/sciadv.adu0601
Publisher
American Association for the Advancement of Science (AAAS)

Description

<jats:p> Muscle satellite cells (MuSCs) respond immediately to environmental cues upon skeletal muscle injuries. Despite decades of research into muscle regeneration, the specific molecular factors that trigger the transition of MuSCs from a quiescent to an active state remain largely unidentified. Here, we identify transient receptor potential melastatin 7 (TRPM7), an Mg <jats:sup>2+</jats:sup> -permeable ion channel, as a critical regulator of MuSC activation. <jats:italic>Trpm7</jats:italic> deletion in MuSCs reduced Mg <jats:sup>2+</jats:sup> influx, impairing myofiber regeneration and leading to decreased MuSC numbers and cell cycle arrest during regeneration. These changes were linked to disrupted mTOR signaling, which drives the transition of MuSCs from G <jats:sub>0</jats:sub> to G <jats:sub>Alert</jats:sub> phase. In addition, <jats:italic>Trpm7</jats:italic> -deficient MuSCs exhibited impaired early responses, including quiescent projection retraction and AP-1 induction. Mg <jats:sup>2+</jats:sup> supplementation rescued these defects, restoring normal MuSC activation. Our findings reveal a previously unrecognized mechanism where Mg <jats:sup>2+</jats:sup> permeation through TRPM7 is essential for MuSC activation and efficient skeletal muscle regeneration, highlighting TRPM7 as a critical regulator of muscle repair. </jats:p>

Journal

  • Science Advances

    Science Advances 11 (14), 2025-04-04

    American Association for the Advancement of Science (AAAS)

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