title: G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.
abstract: 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.
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115; Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
authors.forename: James P
authors.initials: JP
authors.lastname: White
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115; Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
authors.forename: Christiane D
authors.initials: CD
authors.lastname: Wrann
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115; Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Rao
authors.affiliation: Endocrine Research Unit, Division of Endocrinology, The Mayo Clinic, Rochester, MN 55905;
authors.forename: Sreekumaran K
authors.initials: SK
authors.lastname: Nair
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
authors.forename: Mark P
authors.initials: MP
authors.lastname: Jedrychowski
authors.affiliation: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706;
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: You
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, S-171 77, Stockholm, Sweden;
authors.forename: Vicente
authors.initials: V
authors.lastname: Martínez-Redondo
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, S-171 77, Stockholm, Sweden;
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Ruas
authors.affiliation: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706;
authors.forename: Troy A
authors.initials: TA
authors.lastname: Hornberger
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, MA 02139; and.
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, MA 02139; and.
authors.forename: David J
authors.initials: DJ
authors.lastname: Glass
authors.affiliation: Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Piao
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115; Department of Cell Biology, Harvard Medical School, Boston, MA 02115; Bruce_Spiegelman@dfci.harvard.edu.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Spiegelman
mesh_terms: D000818:Animals; D024061:Collagen Type III / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000502:physiology*; D006984:Hypertrophy / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D024061:Collagen Type III; D007334:Insulin-Like Growth Factor I; D009124:Muscle Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; C524781:Adgrg1 protein, mouse; C485290:Ppargc1a protein, mouse; C519530:insulin-like growth factor-1, mouse
keywords: GPR56; Gα12/13; mTOR; muscle hypertrophy; overload