G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.
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.
Duke Scholars
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Related Subject Headings
- Transcription Factors
- Signal Transduction
- Receptors, G-Protein-Coupled
- Physical Conditioning, Animal
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
- Muscle Proteins
- Muscle Fibers, Skeletal
- Mice
- Male
- Insulin-Like Growth Factor I
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcription Factors
- Signal Transduction
- Receptors, G-Protein-Coupled
- Physical Conditioning, Animal
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
- Muscle Proteins
- Muscle Fibers, Skeletal
- Mice
- Male
- Insulin-Like Growth Factor I