REV-ERBα activates the mTOR signalling pathway and promotes myotubes differentiation

Biol Cell. 2020 Aug;112(8):213-221. doi: 10.1111/boc.201900091. Epub 2020 May 7.

Abstract

Background information: Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a master regulator of cell and whole-body energy homoeostasis. REV-ERBα is a nuclear receptor that plays an important role in metabolism. While mTORC1 activation is necessary for muscle differentiation, the role of REV-ERBα is less clear.

Results: We studied the effect of REV-ERBα overexpression and silencing as well as mTORC1 activation and inhibition on the differentiation of C2C12 myoblasts to myotubes. mTOR, myogenin and REV-ERBα were induced during differentiation of myoblasts into myotubes. REV-ERBα was found to activate mTORC1 during the differentiation process even in the absence of the differentiation medium. This activation was presumably through the downregulation of the expression of TSC1, an mTORC1 inhibitor.

Conclusion: Herein we show that REV-ERBα promotes myoblasts differentiation via the activation of the mTORC1 signalling pathway.

Significance: REV-ERBα modulation can activate mTORC1 signalling and promote myoblasts differentiation.

Keywords: C2C12; Differentiation; Myoblasts; Myotubes; REV-ERVα; mTOR.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics*
  • Cell Line
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Mice
  • Muscle Fibers, Skeletal / metabolism*
  • Myoblasts / metabolism
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / genetics
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism*
  • Transfection

Substances

  • Nr1d1 protein, mouse
  • Nuclear Receptor Subfamily 1, Group D, Member 1
  • mTOR protein, mouse
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases
  • Sirolimus