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Publication : Shisa2 regulates the fusion of muscle progenitors.

First Author  Liu Z Year  2018
Journal  Stem Cell Res Volume  31
Pages  31-41 PubMed ID  30007221
Mgi Jnum  J:317909 Mgi Id  MGI:6844653
Doi  10.1016/j.scr.2018.07.004 Citation  Liu Z, et al. (2018) Shisa2 regulates the fusion of muscle progenitors. Stem Cell Res 31:31-41
abstractText  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.
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