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, Guang William Wong, In San Kim, Artur Kania, Michisuke Yuzaki, Michel Bouvier, Jean François Côté

Research output: Contribution to journalArticle

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 (US)
Article number4470
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

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