TY - JOUR
T1 - Spatiotemporal regulation of the GPCR activity of BAI3 by C1qL4 and Stabilin-2 controls myoblast fusion
AU - Hamoud, Noumeira
AU - Tran, Viviane
AU - Aimi, Takahiro
AU - Kakegawa, Wataru
AU - Lahaie, Sylvie
AU - Thibault, Marie Pier
AU - Pelletier, Ariane
AU - Wong, G. William
AU - Kim, In San
AU - Kania, Artur
AU - Yuzaki, Michisuke
AU - Bouvier, Michel
AU - Côté, Jean François
N1 - Funding Information:
We thank Dr. D.R. Hipfner (IRCM) for critical reading of the manuscript. We recognize the technical support of Meirong Liang (IRCM) and expertise of the IRCM Microscopy (Dr. D. Filion) and Mass Spectrometry (Dr. D. Faubert) platforms. We thank Dr. Arhamatoulaye Maiga (IRIC) for guidance in BRET2 experiments. We acknowledge Dr. E.N. Harris (University of Nebraska) for the generous gift of Stabilin-2 plasmid. We acknowledge Dr. T.C. Südhof (Stanford University) for support and sharing reagents. This work was funded by an NIH grant (DK084171) to G.W.W and CIHR grants to J.-F. C. (PJT-153065), M.B. (FDN-148431) and A.K. (MOP-77556 and MOP-97758). N.H. and V.T. are recipients of Ph.D. studentships from the Fonds de Recherche du Québec-Santé (FRQ-S). M.B. holds a Canada Research Chairs in Signal Transduction and Molecular Pharmacology. J.-F.C. is a recipient of a Senior Investigator Award from the FRQ-S and holds the TRANSAT chair in Breast Cancer Research.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-06897-5
DO - 10.1038/s41467-018-06897-5
M3 - Article
C2 - 30367035
AN - SCOPUS:85055614656
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4470
ER -