First Author | White JP | Year | 2014 |
Journal | Proc Natl Acad Sci U S A | Volume | 111 |
Issue | 44 | Pages | 15756-61 |
PubMed ID | 25336758 | Mgi Jnum | J:216660 |
Mgi Id | MGI:5609190 | Doi | 10.1073/pnas.1417898111 |
Citation | White JP, et al. (2014) G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy. Proc Natl Acad Sci U S A 111(44):15756-61 |
abstractText | Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1alpha4) is a protein isoform derived by alternative splicing of the PGC1alpha 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-1alpha4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1alpha4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1alpha4-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 Galpha12/13 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. |