Repression of cell-cell fusion by components of the C-elegans vacuolar ATPase complex
Repression of cell-cell fusion by components of the C-elegans vacuolar ATPase complex
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DOI：
10.1016/j.devcel.2005.02.018
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发表时间：
2005-05-01
影响因子：
11.8
通讯作者：
Rothman, JH
中科院分区：
文献类型：
--
作者：
Kontani, K;Moskowitz, IPG;Rothman, JH
细胞-细胞融合启动受精，在动物发育过程中塑造组织，将干细胞重新编程到新的分化状态，并且可能是癌症进展的关键步骤。虽然细胞融合受到严格调控，但限制融合到合适伴侣的机制尚不清楚。在这里，我们报道了fus-1基因对于抑制秀丽隐杆线虫表皮细胞的融合是必不可少的：在严重的fus-1突变体中，除了侧缝细胞外，所有表皮细胞都不适当地融合成单个大合胞体。这种低灌注需要ef -1，这是表皮细胞融合成离散合胞体所必需的一种完整的膜蛋白。在所有增强融合的表皮细胞中，FUS-1定位于顶质膜，而在未融合的缝细胞中几乎检测不到。fus-1编码液泡H+- atp酶（v - atp酶）的e亚基，其他v - atp酶亚基的缺失也会导致广泛的低灌注。这些发现提高了通过改变v - atp酶活性来操纵细胞融合的可能性。
Cell-cell fusion initiates fertilization, sculpts tissues during animal development, reprograms stem cells to new differentiated states, and may be a key step in cancer progression. While cell fusion is tightly regulated, the mechanisms that limit fusion to appropriate partners are unknown. Here, we report that the fus-1 gene is essential to repress fusion of epidermal cells in C. elegans: in severe fus-1 mutants, all epidermal cells, except the lateral seam cells, inappropriately fuse into a single large syncytium. This hyperfusion requires EFF-1, an integral membrane protein essential for fusion of epidermal cells into discrete syncytia. FUS-1 is localized to the apical plasma membrane in all epidermal cells potentiated to undergo fusion, whereas it is virtually undetectable in nonfusing seam cells. fus-1 encodes the e subunit of the vacuolar H+-ATPase (V-ATPase), and loss of other V-ATPase subunits also causes widespread hyperfusion. These findings raise the possibility of manipulating cell fusion by altering V-ATPase activity.