Shisa2 regulates the fusion of muscle progenitors

Zuojun Liu, Chao Wang, Xiaoqi Liu, Shihuan Kuang

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Adult skeletal muscles are comprised of multinuclear muscle cells called myofibers. During skeletal muscle development and regeneration, mononuclear progenitor cells (myoblasts) fuse to form multinuclear myotubes, which mature and become myofibers. The molecular events mediating myoblast fusion are not fully understood. Here we report that Shisa2, an endoplasmic reticulum (ER) localized protein, regulates the fusion of muscle satellite cell-derived primary myoblasts. Shisa2 expression is repressed by Notch signaling, elevated in activated compared to quiescent satellite cells, and further upregulated during myogenic differentiation. Knockdown of Shisa2 inhibits the fusion of myoblasts without affecting proliferation. Conversely, Shisa2 overexpression in proliferating myoblasts inhibits their proliferation but promotes premature fusion. Interestingly, Shisa2-overexpressing nascent myotubes actively recruit myoblasts to fuse with. At the molecular level, Rac1/Cdc42-mediated cytoskeletal F-actin remodeling is required for Shisa2 to promote myoblast fusion. These results provide a novel mechanism through which an ER protein regulates myogenesis.

Original languageEnglish
Pages (from-to)31-41
Number of pages11
JournalStem Cell Research
Volume31
DOIs
StatePublished - Aug 2018

Bibliographical note

Funding Information:
This work is partially supported by National Institute of Health (NIH) through grant (R01AR071649) to SK, and a grant from National Natural Science Foundation of China (81601215) to ZL.

Funding Information:
This work is partially supported by National Institute of Health (NIH) through grant ( R01AR 071649) to SK, and a grant from National Natural Science Foundation of China ( 81601215 ) to ZL.

Publisher Copyright:
© 2018

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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