The cellular architecture and molecular determinants of the zebrafish fusogenic synapse.

The cellular architecture and molecular determinants of the zebrafish fusogenic synapse.
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斑马鱼融合突触的细胞结构和分子决定因素。

DOI:
10.1016/j.devcel.2022.05.016
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发表时间:
2022-07-11
期刊:
影响因子:
11.8
通讯作者:
Chen, Elizabeth H.
Chen, Elizabeth H.
中科院分区:
生物学1区
文献类型:
--
作者:
Luo, Zhou;Shi, Jun;Pandey, Pratima;Ruan, Zhi-Rong;Sevdali, Maria;Bu, Ye;Lu, Yue;Du, Shaojun;Chen, Elizabeth H.

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成肌细胞融合是骨骼肌发育和再生中不可缺少的过程。在果蝇中的研究导致了不对称融合突触的发现,其中一个细胞用肌动蛋白推进的膜突起侵入其融合伴侣以促进融合。然而,脊椎动物成肌细胞融合的时间和地点仍然难以捉摸。在这里,我们表明,斑马鱼快肌细胞之间的融合是由富F-肌动蛋白的侵入性结构介导的。两种细胞粘附分子Jam 2a和Jam 3b与肌动蛋白结构相关,其中Jam 2a是主要的组织者。Arp 2/3肌动蛋白成核促进因子WAVE和WASP,而不是双向融合蛋白Myomaker或Myomixer,促进侵入性结构的形成。此外,融合蛋白微区和侵入性突起的会聚是细胞膜融合的先决条件。因此,我们的研究提供了前所未有的见解的细胞结构和分子决定因素的不对称融合突触在一个完整的脊椎动物。Luo等人证明了在斑马鱼快肌细胞之间的融合位点处的富含F-肌动蛋白的侵入性结构。这种结构的形成是由细胞粘附触发的,并由肌动蛋白成核促进因子促进。这项研究揭示了在一个完整的脊椎动物的不对称融合突触。
Myoblast fusion is an indispensable process in skeletal muscle development and regeneration. Studies in Drosophila led to the discovery of the asymmetric fusogenic synapse, where 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. Luo et al. demonstrate an F-actin-enriched invasive structure at the site of fusion between zebrafish fast muscle cells. The formation of this structure is triggered by cell adhesion and promoted by actin nucleation-promoting factors. This study reveals the asymmetric fusogenic synapse in an intact vertebrate animal.
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