Myoblast fusion is an indispensable process in skeletal muscle development and regeneration. Studies in Drosophila led to the discovery of the asymmetric fusogenic synapse, in which one cell invades its fusion partner with actin-propelled membrane protrusions to promote fusion. However, the timing and sites of vertebrate myoblast fusion remain elusive. Here, we show that fusion between zebrafish fast muscle cells is mediated by an F-actin-enriched invasive structure. Two cell adhesion molecules, Jam2a and Jam3b, are associated with the actin structure, with Jam2a being the major organizer. The Arp2/3 actin nucleation-promoting factors, WAVE and WASP—but not the bipartite fusogenic proteins, Myomaker or Myomixer—promote the formation of the invasive structure. Moreover, the convergence of fusogen-containing microdomains and the invasive protrusions is a prerequisite for cell membrane fusion. Thus, our study provides unprecedented insights into the cellular architecture and molecular determinants of the asymmetric fusogenic synapse in an intact vertebrate animal.

成肌细胞融合是骨骼肌发育和再生中不可或缺的过程。果蝇研究导致了不对称融合突触的发现，其中一个细胞通过肌动蛋白推动的膜突起侵入其融合伙伴以促进融合。然而，脊椎动物成肌细胞融合的时间和部位仍然难以捉摸。在这里，我们证明斑马鱼快肌细胞之间的融合是由富含 F-肌动蛋白的侵入结构介导的。两种细胞粘附分子 Jam2a 和 Jam3b 与肌动蛋白结构相关，其中 Jam2a 是主要组织者。Arp2/3 肌动蛋白成核促进因子 WAVE 和 WASP（但不是二分融合蛋白 Myomaker 或 Myomixer）促进侵入结构的形成。此外，含有融合剂的微区和侵入性突起的融合是细胞膜融合的先决条件。因此，