G protein coupled receptor 56 is a target gene of the PGC-1α4 isoform and regulates overload-induced muscle hypertrophy (1163.15)

The PGC-1α isoform referred to as PGC-1α4 has recently been shown to promote muscle hypertrophy and attenuate muscle wasting. Although it has been shown that PGC-1α4 can regulate the expression of IGF-1 and myostatin, two potent regulators of muscle mass, its detailed mechanism of action remains unclear. Gene array analysis has identified the G-protein coupled receptor 56 to be a transcriptional target of PGC-1α4. GPR56 is a newly defined adhesion receptor which can mediate both G protein coupled signalling and integrin function, although little in know about its function in skeletal muscle. We have found the anabolic effect of PGC-1α4 is, in part dependent on GPR56 signalling as knockdown of GPR56 attenuates PGC-1α4-induced muscle hypertrophy in vitro. Forced expression of GPR56 in primary myotubes results in mild hypertrophy. However, when forced expression of GPR56 is accompanied by the addition of its ligand, Collagen III, it drives robust myotube hypertrophy. In vivo models of overload-induced muscle...