Proceedings of the National Academy of Sciences - PNAS, 2014-11, Vol.111 (44), p.15756-15761
2014
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2014-11, Vol.111 (44), p.15756-15761
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. Significance The work reported in this paper describes a previously unknown signaling pathway in skeletal muscle acting through G protein-coupled receptor 56-Galpha12/13. This discovery elucidates a previously unknown mechanism of muscle anabolism and gives another target of investigation for therapies against the loss of muscle mass seen with aging and various wasting diseases.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424, 1091-6490eISSN: 1091-6490DOI: 10.1073/pnas.1417898111Titel-ID: cdi_pubmed_primary_25336758
- Format
- –
- Schlagworte
- Animals, Biological Sciences, Collagen, Collagen Type III - biosynthesis, Collagens, Exercise, Gene expression, Gene Expression Regulation - physiology, Hypertrophy, Hypertrophy - metabolism, Insulin-Like Growth Factor I - biosynthesis, Male, Medicin och hälsovetenskap, Messenger RNA, Mice, MicroRNAs, Muscle fibers, Muscle Fibers, Skeletal - metabolism, Muscle Proteins - metabolism, Muscles, Muscular system, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Physical Conditioning, Animal, Physiological regulation, Protein isoforms, Protein synthesis, Proteins, Receptors, Receptors, G-Protein-Coupled - biosynthesis, Signal Transduction - physiology, Skeletal muscle, Transcription factors, Transcription Factors - metabolism