G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.

Journal Article (Journal Article)

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1α4) is a protein isoform derived by alternative splicing of the PGC1α mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56) is a transcriptional target of PGC-1α4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1α4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1α4-induced muscle hypertrophy in vitro. Forced expression of GPR56 results in myotube hypertrophy through the expression of insulin-like growth factor 1, which is dependent on Gα12/13 signaling. A murine model of overload-induced muscle hypertrophy is associated with increased expression of both GPR56 and its ligand collagen type III, whereas genetic ablation of GPR56 expression attenuates overload-induced muscle hypertrophy and associated anabolic signaling. These data illustrate a signaling pathway through GPR56 which regulates muscle hypertrophy associated with resistance/loading-type exercise.

Full Text

Duke Authors

Cited Authors

  • White, JP; Wrann, CD; Rao, RR; Nair, SK; Jedrychowski, MP; You, J-S; Martínez-Redondo, V; Gygi, SP; Ruas, JL; Hornberger, TA; Wu, Z; Glass, DJ; Piao, X; Spiegelman, BM

Published Date

  • November 4, 2014

Published In

Volume / Issue

  • 111 / 44

Start / End Page

  • 15756 - 15761

PubMed ID

  • 25336758

Pubmed Central ID

  • PMC4226111

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1417898111


  • eng

Conference Location

  • United States