The IRE1α/XBP1 signaling axis drives myoblast fusion in adult skeletal muscle

DOI DOI Web Site Web Site 研究データあり 参考文献69件 オープンアクセス

書誌事項

公開日
2024-07-09
資源種別
journal article
権利情報
  • https://creativecommons.org/licenses/by/4.0
  • https://creativecommons.org/licenses/by/4.0
DOI
  • 10.1038/s44319-024-00197-4
  • 10.1101/2023.09.26.559625
公開者
Springer Science and Business Media LLC

説明

<jats:title>Abstract</jats:title> <jats:p> Skeletal muscle regeneration involves a signaling network that regulates the proliferation, differentiation, and fusion of muscle precursor cells to injured myofibers. IRE1α, one of the arms of the unfolded protein response, regulates cellular proteostasis in response to ER stress. Here, we demonstrate that inducible deletion of IRE1α in satellite cells of mice impairs skeletal muscle regeneration through inhibiting myoblast fusion. Knockdown of IRE1α or its downstream target, X-box protein 1 (XBP1), also inhibits myoblast fusion during myogenesis. Transcriptome analysis revealed that knockdown of IRE1α or XBP1 dysregulates the gene expression of molecules involved in myoblast fusion. The IRE1α-XBP1 axis mediates the gene expression of multiple profusion molecules, including myomaker ( <jats:italic>Mymk</jats:italic> ). Spliced XBP1 (sXBP1) transcription factor binds to the promoter of <jats:italic>Mymk</jats:italic> gene during myogenesis. Overexpression of myomaker in IRE1α-knockdown cultures rescues fusion defects. Inducible deletion of IRE1α in satellite cells also inhibits myoblast fusion and myofiber hypertrophy in response to functional overload. Collectively, our study demonstrates that IRE1α promotes myoblast fusion through sXBP1-mediated up-regulation of the gene expression of multiple profusion molecules, including myomaker. </jats:p>

収録刊行物

  • EMBO Reports

    EMBO Reports 25 (8), 3627-3650, 2024-07-09

    Springer Science and Business Media LLC

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