title: G-protein coupled receptor BAI3 promotes myoblast fusion in vertebrates.
abstract: Muscle fibers form as a result of myoblast fusion, yet the cell surface receptors regulating this process are unknown in vertebrates. In Drosophila, myoblast fusion involves the activation of the Rac pathway by the guanine nucleotide exchange factor Myoblast City and its scaffolding protein ELMO, downstream of cell-surface cell-adhesion receptors. We previously showed that the mammalian ortholog of Myoblast City, DOCK1, functions in an evolutionarily conserved manner to promote myoblast fusion in mice. In search for regulators of myoblast fusion, we identified the G-protein coupled receptor brain-specific angiogenesis inhibitor (BAI3) as a cell surface protein that interacts with ELMO. In cultured cells, BAI3 or ELMO1/2 loss of function severely impaired myoblast fusion without affecting differentiation and cannot be rescued by reexpression of BAI3 mutants deficient in ELMO binding. The related BAI protein family member, BAI1, is functionally distinct from BAI3, because it cannot rescue the myoblast fusion defects caused by the loss of BAI3 function. Finally, embryonic muscle precursor expression of a BAI3 mutant unable to bind ELMO was sufficient to block myoblast fusion in vivo. Collectively, our findings provide a role for BAI3 in the relay of extracellular fusion signals to their intracellular effectors, identifying it as an essential transmembrane protein for embryonic vertebrate myoblast fusion.
authors.affiliation: Institut de Recherches Cliniques de Montréal, Montreal, QC, Canada H2W 1R7.
authors.forename: Noumeira
authors.initials: N
authors.lastname: Hamoud
authors.forename: Viviane
authors.initials: V
authors.lastname: Tran
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Croteau
authors.forename: Artur
authors.initials: A
authors.lastname: Kania
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Côté
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002459:Cell Fusion; D002460:Cell Line; D002642:Chick Embryo; D018274:Electroporation; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008565:Membrane Proteins; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology*; D032446:Myoblasts / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: C484729:Adgrb3 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled
keywords: RhoGTP; ced-12; model system; myogenesis; myotube formation