Spectraplakin Induces Positive Feedback between Fusogens and the Actin Cytoskeleton to Promote Cell-Cell Fusion
Spectraplakin Induces Positive Feedback between Fusogens and the Actin Cytoskeleton to Promote Cell-Cell Fusion
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Spectraplakin 诱导融合剂和肌动蛋白细胞骨架之间的正反馈，以促进细胞与细胞的融合
DOI：
10.1016/j.devcel.2017.03.006
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发表时间：
2017-04-10
影响因子：
11.8
通讯作者：
Ou, Guangshuo
中科院分区：
文献类型：
--
作者：
Yang, Yihong;Zhang, Yan;Ou, Guangshuo
细胞-细胞融合通常需要细胞融合蛋白和肌动蛋白驱动的膜突起。然而，融合剂和肌动蛋白细胞骨架之间的分子联系仍不清楚。在这里，我们发现秀丽隐杆线虫融合剂 EFF-1 和 F-肌动蛋白在胚胎后融合细胞的皮层富集，WASP 和 Arp2/3 的条件突变通过损害 EFF-1 定位来延迟细胞与细胞的融合。我们的亲和纯化和质谱分析确定肌动蛋白结合蛋白spectrumplakin/VAB-10A 与EFF-1 结合。 VAB-10A 通过将 EFF-1 连接到肌动蛋白细胞骨架来促进细胞与细胞的融合。相反，EFF-1在体外增强了VAB-10A的F-肌动蛋白成束活性，并且在eff-1或vab-10a突变体中皮质中的肌动蛋白动力学降低。因此，细胞-细胞融合是通过正反馈环路促进的，其中通过spectrumplakin交联以将融合剂招募到融合位点的肌动蛋白丝通过融合剂得到增强，从而增加融合剂进一步积累以形成融合突触的可能性。
Cell-cell fusion generally requires cellular fusogenic proteins and actin-propelled membrane protrusions. However, the molecular connections between fusogens and the actin cytoskeleton remain unclear. Here, we show that the Caenorhabditis elegans fusogen EFF-1 and F-actin are enriched at the cortex of the post-embryonic fusing cells, and conditional mutations of WASP and Arp2/3 delay cell-cell fusion by impairing EFF-1 localization. Our affinity purification and mass spectrometry analyses determined that an actin-binding protein, spectraplakin/VAB-10A, binds to EFF-1. VAB-10A promotes cell-cell fusion by linking EFF-1 to the actin cytoskeleton. Conversely, EFF-1 enhanced the F-actin bundling activity of VAB-10A in vitro, and actin dynamics in the cortex were reduced in eff-1 or vab-10a mutants. Thus, cell-cell fusion is promoted by a positive feedback loop in which actin filaments that are crosslinked by spectraplakin to recruit fusogens to fusion sites are reinforced via fusogens, thereby increasing the probability of further fusogen accumulation to form fusion synapses.