Spatiotemporal regulation of the GPCR activity of BAI3 by C1qL4 and Stabilin-2 controls myoblast fusion

Noumeira Hamoud, Viviane Tran, Takahiro Aimi, Wataru Kakegawa, Sylvie Lahaie, Marie Pier Thibault, Ariane Pelletier, G. William Wong, In-San Kim, Artur Kania, Michisuke Yuzaki, Michel Bouvier, Jean François Côté

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12 Citations (Scopus)

Abstract

Myoblast fusion is tightly regulated during development and regeneration of muscle fibers. BAI3 is a receptor that orchestrates myoblast fusion via Elmo/Dock1 signaling, but the mechanisms regulating its activity remain elusive. Here we report that mice lacking BAI3 display small muscle fibers and inefficient muscle regeneration after cardiotoxin-induced injury. We describe two proteins that repress or activate BAI3 in muscle progenitors. We find that the secreted C1q-like1–4 proteins repress fusion by specifically interacting with BAI3. Using a proteomic approach, we identify Stabilin-2 as a protein that interacts with BAI3 and stimulates its fusion promoting activity. We demonstrate that Stabilin-2 activates the GPCR activity of BAI3. The resulting activated heterotrimeric G-proteins contribute to the initial recruitment of Elmo proteins to the membrane, which are then stabilized on BAI3 through a direct interaction. Collectively, our results demonstrate that the activity of BAI3 is spatiotemporally regulated by C1qL4 and Stabilin-2 during myoblast fusion.

Original languageEnglish
Article number4470
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Hamoud, N., Tran, V., Aimi, T., Kakegawa, W., Lahaie, S., Thibault, M. P., Pelletier, A., Wong, G. W., Kim, I-S., Kania, A., Yuzaki, M., Bouvier, M., & Côté, J. F. (2018). Spatiotemporal regulation of the GPCR activity of BAI3 by C1qL4 and Stabilin-2 controls myoblast fusion. Nature communications, 9(1), [4470]. https://doi.org/10.1038/s41467-018-06897-5