Corrigendum: Defining functional interactions during biogenesis of epithelial junctions.
Corrigendum: Defining functional interactions during biogenesis of epithelial junctions.
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DOI：
10.1038/ncomms14195
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发表时间：
2017-01-05
影响因子：
16.6
通讯作者：
Braga VM
中科院分区：
文献类型：
--
作者：
Erasmus JC;Bruche S;Pizarro L;Maimari N;Poggioli T;Tomlinson C;Lees J;Zalivina I;Wheeler A;Alberts A;Russo A;Braga VM
尽管最近取得了广泛的进展，但对肌动蛋白细胞骨架重塑如何支持稳定连接的全面理解仍有待建立。在这里，我们设计了一个平台，整合肌动蛋白功能与优化的表型聚类和识别新的细胞骨架蛋白，其功能层次和途径，调节E-钙粘蛋白粘附。耗尽EEF 1A，肌动蛋白捆绑蛋白，增加E-钙粘蛋白的水平在交界处没有相应的加强细胞-细胞接触。这个意想不到的结果反映了EEF 1A耗尽细胞中更动态和移动的连接肌动蛋白。EEF 1A在钙粘蛋白接触维持中的伙伴是与EEF 1A相互作用的EIFDIAPH 2。相反，内吞调节剂TRIP 10或Rho GTd 3激活剂VAV 2的耗竭降低了连接处的E-钙粘蛋白水平。TRIP 10结合至VAV 2并需要VAV 2功能用于其连接定位。总的来说，我们提出了新的概念性见解连接稳定，整合已知的和新的途径与上皮形态发生，稳态和疾病的影响。
In spite of extensive recent progress, a comprehensive understanding of how actin cytoskeleton remodelling supports stable junctions remains to be established. Here we design a platform that integrates actin functions with optimized phenotypic clustering and identify new cytoskeletal proteins, their functional hierarchy and pathways that modulate E-cadherin adhesion. Depletion of EEF1A, an actin bundling protein, increases E-cadherin levels at junctions without a corresponding reinforcement of cell–cell contacts. This unexpected result reflects a more dynamic and mobile junctional actin in EEF1A-depleted cells. A partner for EEF1A in cadherin contact maintenance is the formin DIAPH2, which interacts with EEF1A. In contrast, depletion of either the endocytic regulator TRIP10 or the Rho GTPase activator VAV2 reduces E-cadherin levels at junctions. TRIP10 binds to and requires VAV2 function for its junctional localization. Overall, we present new conceptual insights on junction stabilization, which integrate known and novel pathways with impact for epithelial morphogenesis, homeostasis and diseases.