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  3. The adhesion G-protein-coupled receptor Gpr116 is essential to maintain the skeletal muscle stem cell pool

The adhesion G-protein-coupled receptor Gpr116 is essential to maintain the skeletal muscle stem cell pool

  • Cell Rep. 2022 Nov 15;41(7):111645. doi: 10.1016/j.celrep.2022.111645.
Charlotte Sénéchal 1,  Ryo Fujita 1,  Solène Jamet 2,  Arhamatoulaye Maiga 3,  Junio Dort 4,  Zakaria Orfi 4,  Nicolas A Dumont 5,  Michel Bouvier 3,  Colin Crist 6
Affiliations

Affiliations

  • 1 Department of Human Genetics, McGill University, 3640 University St., Montréal, QC H3A 0C7, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin de la Cote Ste. Catherine, Montréal, QC H3T 1E2, Canada.
  • 2 Department of Human Genetics, McGill University, 3640 University St., Montréal, QC H3A 0C7, Canada.
  • 3 Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, QC H3T 1J4, Canada.
  • 4 CHU Sainte-Justine Research Center, Montréal, QC, Canada.
  • 5 CHU Sainte-Justine Research Center, Montréal, QC, Canada; Université de Montréal, Faculty of Medicine, School of Rehabilitation, Montréal, QC, Canada.
  • 6 Department of Human Genetics, McGill University, 3640 University St., Montréal, QC H3A 0C7, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin de la Cote Ste. Catherine, Montréal, QC H3T 1E2, Canada. Electronic address: [email protected].
PMID: 36384129 DOI: 10.1016/j.celrep.2022.111645
Abstract

Skeletal muscle is populated with a reservoir of quiescent muscle stem cells (MuSCs), which regenerate the tissue after injury. Here, we show that the adhesion G-protein-coupled receptor Gpr116 is essential for long-term maintenance of the MuSC pool. Quiescent MuSCs express high levels of Gpr116, which is rapidly downregulated upon MuSC activation. MuSCs deficient for Gpr116 exhibit progressive depletion over time and are defective in self-renewal. Adhesion G-protein-coupled receptors contain an agonistic peptide sequence, called the "Stachel" sequence, within their long N-terminal ectodomains. Stimulation of MuSCs with the GPR116 Stachel peptide delays MuSC activation and differentiation. Stachel peptide stimulation of GPR116 leads to strong interaction with β-arrestins. Stimulation of GPR116 increases the nuclear localization of β-arrestin1, where it interacts with cAMP response element binding protein to regulate gene expression. Altogether, we propose a model by which GPR116 maintains the MuSC pool via nuclear functions of β-arrestin1.

Keywords

CP: Stem cell research; GPR116; adhesion G-protein-coupled receptor; muscle stem cell; regeneration; skeletal muscle; β-arrestin1.

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