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.
|Number of pages||11|
|Journal||Stem Cell Research|
|State||Published - Aug 2018|
Bibliographical noteFunding 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.
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.
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology