Stac3 inhibits myoblast differentiation into myotubes.
The functionally undefined Stac3 gene, predicted to encode a SH3 domain- and C1 domain-containing protein, was recently found to be specifically expressed in skeletal muscle and essential to normal skeletal muscle development and contraction. In this study we determined the potential role of Stac3 in myoblast proliferation and differentiation, two important steps of muscle development. Neither siRNA-mediated Stac3 knockdown nor plasmid-mediated Stac3 overexpression affected the proliferation of C2C12 myoblasts. Stac3 knockdown promoted the differentiation of C2C12 myoblasts into myotubes as evidenced by increased fusion index, increased number of nuclei per myotube, and increased mRNA and protein expression of myogenic markers including myogenin and myosin heavy chain. In contrast, Stac3 overexpression inhibited the differentiation of C2C12 myoblasts into myotubes as evidenced by decreased fusion index, decreased number of nuclei per myotube, and decreased mRNA and protein expression of myogenic markers. Compared to wild-type myoblasts, myoblasts from Stac3 knockout mouse embryos showed accelerated differentiation into myotubes in culture as evidenced by increased fusion index, increased number of nuclei per myotube, and increased mRNA expression of myogenic markers. Collectively, these data suggest an inhibitory role of endogenous Stac3 in myoblast differentiation. Myogenesis is a tightly controlled program; myofibers formed from prematurely differentiated myoblasts are dysfunctional. Thus, Stac3 may play a role in preventing precocious myoblast differentiation during skeletal muscle development.
Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, Virginia, United States of America.
Xiaomei
X
Ge
Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, Virginia, United States of America.
Yafei
Y
Zhang
Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, Virginia, United States of America.
Sungwon
S
Park
Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, Virginia, United States of America.
Xiaofei
X
Cong
Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, Virginia, United States of America.
David E
DE
Gerrard
Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, Virginia, United States of America.
Honglin
H
Jiang
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D017931:DNA Primers; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology*; D032446:Myoblasts / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D016133:Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D009419:Nerve Tissue Proteins; C583601:STAC3 protein, mouse