Spatiotemporal regulation of the GPCR activity of BAI3 by C1qL4 and Stabilin-2 controls myoblast fusion.
Spatiotemporal regulation of the GPCR activity of BAI3 by C1qL4 and Stabilin-2 controls myoblast fusion.
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DOI：
10.1038/s41467-018-06897-5
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发表时间：
2018-10-26
影响因子：
16.6
通讯作者：
Côté JF
中科院分区：
文献类型：
--
作者：
Hamoud N;Tran V;Aimi T;Kakegawa W;Lahaie S;Thibault MP;Pelletier A;Wong GW;Kim IS;Kania A;Yuzaki M;Bouvier M;Côté JF
成肌细胞融合在肌纤维的发育和再生过程中受到严格的调节。BAI 3是一种通过埃尔莫/Dock 1信号传导协调成肌细胞融合的受体，但调节其活性的机制仍不清楚。在这里，我们报告说，小鼠缺乏BAI 3显示小肌肉纤维和低效的肌肉再生后，心脏毒素诱导的损伤。我们描述了两种抑制或激活肌肉祖细胞中BAI 3的蛋白质。我们发现分泌的C1 q样1 -4蛋白通过与BAI 3特异性相互作用来抑制融合。使用蛋白质组学方法，我们确定稳定蛋白2作为与BAI 3相互作用并刺激其融合促进活性的蛋白质。我们证明稳定蛋白-2激活BAI 3的GPCR活性。所得到的活化的异源三聚体G蛋白有助于埃尔莫蛋白最初募集到膜上，然后通过直接相互作用稳定在BAI 3上。总的来说，我们的研究结果表明，BAI 3的活动是时空调节的C1 qL 4和稳定蛋白-2在成肌细胞融合。成肌细胞融合是肌肉生长和再生的重要步骤，并由G蛋白偶联受体（GPCR）BAI 3调节。Hamoud等人在此表明，BAI 3的GPCR活性在成肌细胞融合过程中受到时空调节，并将C1 qL 4和Stabilin-2分别鉴定为其活性的负调节剂和正调节剂。
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. Myoblast fusion is an essential step in muscle growth and regeneration, and is regulated by the G-protein coupled receptor (GPCR) BAI3. Here Hamoud et al. show that the GPCR activity of BAI3 is spatiotemporally regulated during myoblast fusion, and identify C1qL4 and Stabilin-2 as, respectively, negative and positive regulators of its activity.
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影响因子：
64.5
作者：
Fritsch R;de Krijger I;Fritsch K;George R;Reason B;Kumar MS;Diefenbacher M;Stamp G;Downward J
通讯作者：
Downward J
影响因子：
4
作者：
Kim JH;Jin P;Duan R;Chen EH
通讯作者：
Chen EH
影响因子：
21.3
作者：
Côté, JF;Motoyama, AB;Vuori, K
通讯作者：
Vuori, K
影响因子：
11.4
作者：
Arac, Demet;Boucard, Antony A.;Bolliger, Marc F.;Nguyen, Jenna;Soltis, S. Michael;Suedhof, Thomas C.;Brunger, Axel T.
通讯作者：
Brunger, Axel T.
DOI：
10.1073/pnas.1313886111
发表时间：
2014-03-11
影响因子：
11.1
作者：
Hamoud, Noumeira;Tran, Viviane;Cote, Jean-Francois
通讯作者：
Cote, Jean-Francois