The Triple-Repeat Protein Anakonda Controls Epithelial Tricellular Junction Formation in Drosophila
The Triple-Repeat Protein Anakonda Controls Epithelial Tricellular Junction Formation in Drosophila
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DOI：
10.1016/j.devcel.2015.03.023
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发表时间：
2015-06-08
影响因子：
11.8
通讯作者：
Luschnig, Stefan
中科院分区：
文献类型：
--
作者：
Byri, Sunitha;Misra, Tvisha;Luschnig, Stefan
在上皮中，特化的三细胞连接（TCJ）介导三细胞顶点处的细胞接触。TCJ是上皮生物学和疾病的基础，但只有少数TCJ组分是已知的，它们如何在三细胞顶点组装尚不清楚。在这里，我们描述了一种跨膜蛋白，Anakonda（阿卡），它定位于TCJs和是必不可少的形成的三细胞，但不是双细胞，在果蝇的路口。Aka的缺失导致与不规则TCJ结构和几何形状相关的上皮屏障缺陷，表明Aka组织细胞角。Aka是必要的和足够的积累Gliotactin在TCJ，这表明Aka启动TCJ组装招募其他蛋白质的三细胞顶点。阿卡的胞外结构域有一个不寻常的三重重复结构，可以介导自组装，由三细胞顶点的几何形状。相反，Aka的胞质尾区对于TCJ定位是不稳定的。因此，细胞外的相互作用，而不是TCJ定向的细胞内运输，似乎介导TCJ组装。
In epithelia, specialized tricellular junctions (TCJs) mediate cell contacts at three-cell vertices. TCJs are fundamental to epithelial biology and disease, but only a few TCJ components are known, and how they assemble at tricellular vertices is not understood. Here we describe a transmembrane protein, Anakonda (Aka), which localizes to TCJs and is essential for the formation of tricellular, but not bicellular, junctions in Drosophila. Loss of Aka causes epithelial barrier defects associated with irregular TCJ structure and geometry, suggesting that Aka organizes cell corners. Aka is necessary and sufficient for accumulation of Gliotactin at TCJs, suggesting that Aka initiates TCJ assembly by recruiting other proteins to tricellular vertices. Aka's extracellular domain has an unusual tripartite repeat structure that may mediate self-assembly, directed by the geometry of tricellular vertices. Conversely, Aka's cytoplasmic tail is dispensable for TCJ localization. Thus, extracellular interactions, rather than TCJ-directed intracellular transport, appear to mediate TCJ assembly.