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The RapGEF PDZ-GEF2 is required for maturation of cell-cell junctions

机译：RapGEF PDZ-GEF2是细胞间连接成熟所必需的

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摘要

The small G-protein Rap1 is a critical regulator of cell-cell contacts and is activated by the remodeling of adherens junctions. Here we identify the Rap1 guanine nucleotide exchange factor PDZ-GEF2 as an upstream activator of Rap1 required for the maturation of adherens junctions in the lung carcinoma cells A549. Knockdown of PDZ-GEF2 results in the persistence of adhesion zippers at cell-cell contacts. Activation of Rap1A rescues junction maturation in absence of PDZ-GEF2, demonstrating that Rap1A is downstream of PDZ-GEF2 in this process. Moreover, depletion of Rap1A, but not Rap1B, impairs adherens junction maturation. siRNA for PDZ-GEF2 also lowers the levels of E-cadherin, an effect that can be mimicked by Rap1B, but not Rap1A siRNA. Since junctions in Rap1B depleted cells have a mature appearance, these data suggest that PDZ-GEF2 activates Rap1A and Rap1B to perform different functions. Our results present the first direct evidence that PDZ-GEF2 plays a critical role in the maturation of adherens junctions. (C) 2008 Elsevier Inc. All rights reserved.

机译：小G蛋白Rap1是细胞与细胞接触的关键调节剂，并通过粘附连接的重塑而激活。在这里，我们确定Rap1鸟嘌呤核苷酸交换因子PDZ-GEF2作为Rap1的上游激活剂，对于肺癌细胞A549中的黏附连接成熟而言是必需的。击倒PDZ-GEF2会导致粘附拉链在细胞与细胞之间持续存在。 Rap1A的激活可在不存在PDZ-GEF2的情况下挽救接头成熟，这表明Rap1A在此过程中位于PDZ-GEF2的下游。此外，Rap1A而不是Rap1B的消耗会削弱粘附连接的成熟度。 PDZ-GEF2的siRNA也会降低E-钙粘蛋白的水平，Rap1B可以模仿这种效果，但Rap1A siRNA不能。由于Rap1B耗尽的细胞中的连接具有成熟的外观，这些数据表明PDZ-GEF2激活Rap1A和Rap1B以执行不同的功能。我们的结果提供了第一个直接证据，PDZ-GEF2在粘附连接的成熟中起关键作用。（C）2008 Elsevier Inc.保留所有权利。

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来源
《Cellular Signalling》 |2008年第9期|共8页
作者
Dube N; Kooistra MRH; Pannekoek WJ; Vliem MJ; Oorschot V; Klumperman J; Rehmann H; Bos JL;
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正文语种 eng
中图分类细胞形态学;
关键词
Rap1; PDZ-GEF2; adherens junction; E-cadherin; VASCULAR ENDOTHELIAL CADHERIN; NUCLEOTIDE-EXCHANGE FACTOR; SMALL G-PROTEIN; BARRIER FUNCTION; BETA-CATENIN; CAENORHABDITIS-ELEGANS; SCAFFOLDING MOLECULE; LOCAL CONCENTRATION; CYCLIC-AMP; ADHESION;

机译：Rap1;PDZ-GEF2;粘附连接;E-钙粘着蛋白;血管内皮钙粘蛋白;核苷酸交换因子;小G蛋白;屏障功能;贝塔-连环蛋白;食蟹鱼-粘蛋白;脚手架分子;局部浓缩;

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专利

1. The RapGEF PDZ-GEF2 is required for maturation of cell-cell junctions [J] . Dube N, Kooistra MRH, Pannekoek WJ, Cellular Signalling . 2008,第9期

机译：RapGEF PDZ-GEF2是细胞间连接成熟所必需的
2. The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts [J] . Cara J. Gottardi, Monique Arpin, Alan S. Fanning Proceedings of the National Academy of Sciences of the United States of America . 1996,第20期

机译：连接相关蛋白zonula occludens-1，在成熟之前和细胞与细胞之间的重塑过程中定位于细胞核。
3. Interferon Regulatory Factor 6 is required for proper cell-cell junctions [J] . Antiguas A., Sander E. A., Halberg S., The Journal of investigative dermatology. . 2019,第5Suppla1期

机译：适当的细胞 - 细胞连接需要干扰素调节因子6
4. Measurement of mechanical forces at epithelial cell-cell junctions and the nuclear LINC complex [C] . Daniel Conway 第31回バイオエンジニアリング講演会論文集 . 2018

机译：测量上皮细胞间连接和核LINC复合体的机械力
5. Convergently-evolved peptide-based cell-cell signaling system required for virulence of a eukaryotic pathogen. [D] . Homer, Christina M. 2016

机译：真核病原体毒力所需的基于进化的肽基细胞信号系统。
6. The junction-associated protein zonula occludens-1 localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts. [O] . C J Gottardi, M Arpin, A S Fanning, 1996

机译：连接相关蛋白小带闭合蛋白-1在成熟之前和细胞与细胞接触的重塑过程中定位于细胞核。
7. The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts. [O] . Gottardi, C J, Arpin, M, Fanning, A S, 1996

机译：连接相关蛋白，小带闭合蛋白-1，在成熟之前和细胞与细胞接触的重塑过程中定位于细胞核。

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