TY - JOUR
T1 - Shisa2 regulates the fusion of muscle progenitors
AU - Liu, Zuojun
AU - Wang, Chao
AU - Liu, Xiaoqi
AU - Kuang, Shihuan
N1 - Publisher Copyright:
© 2018
PY - 2018/8
Y1 - 2018/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85049651749&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049651749&partnerID=8YFLogxK
U2 - 10.1016/j.scr.2018.07.004
DO - 10.1016/j.scr.2018.07.004
M3 - Article
C2 - 30007221
AN - SCOPUS:85049651749
SN - 1873-5061
VL - 31
SP - 31
EP - 41
JO - Stem Cell Research
JF - Stem Cell Research
ER -