Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells.
Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells.
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DOI：
10.1083/jcb.200605012
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发表时间：
2006-10-09
影响因子：
7.8
通讯作者：
Takeichi, Masatoshi
中科院分区：
文献类型：
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作者：
Otani, Tetsuhisa;Ichii, Tetsuo;Aono, Shinya;Takeichi, Masatoshi
上皮细胞通常呈蜂窝状排列，最大限度地减少了细胞与细胞的接触面积，这表明一些张力作用于细胞边界的形成。然而，产生这种张力的分子机制仍不清楚。我们发现，Tuba通过与ZO-1的相互作用，集中在简单上皮细胞连接的顶端。RNAi介导的Tuba的耗尽改变了细胞连接的几何形状，导致了弯曲和松弛的外观。在亚细胞水平上，Tuba的失活改变了连接的F-肌动蛋白和E-钙粘蛋白的组装模式。在钙交换实验中，tuba RNAi也可以延缓细胞连接的形成。抑制CdC42的活性或耗尽作为Cdc42的效应子的N-WASP，模拟了Tuba耗竭的影响。相反，显性活性的Cdc42或N-WASP的过表达促进了Tuba缺失细胞的连接形成。这些结果表明，Tuba通过局部激活CDC42及其效应器来控制细胞连接的形成。
Epithelial cells are typically arranged in a honeycomb-like pattern, minimizing their cell–cell contact areas, which suggests that some tension operates for shaping of the cell boundaries. However, the molecular mechanisms that generate such tension remain unknown. We found that Tuba, which is a Cdc42-specific GEF, was concentrated at the apical-most region of cell junctions in simple epithelia via its interaction with ZO-1. RNAi–mediated depletion of Tuba altered the geometrical configuration of cell junctions, resulting in a curved and slack appearance. At the subcellular level, Tuba inactivation modified the assembly pattern of junctional F-actin and E-cadherin. Tuba RNAi also retarded cell junction formation in calcium-switch experiments. Suppression of Cdc42 activity or depletion of N-WASP, which is an effector of Cdc42, mimicked the effects of Tuba depletion. Conversely, overexpression of dominant-active Cdc42 or N-WASP enhanced the junction formation of Tuba-depleted cells. These results suggest that Tuba controls the shaping of cell junctions through the local activation of Cdc42 and its effectors.