PALS1 specifies the localization of ezrin to the apical membrane of gastric parietal cells
PALS1 specifies the localization of ezrin to the apical membrane of gastric parietal cells
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DOI：
10.1074/jbc.m411941200
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发表时间：
2005-04-08
影响因子：
4.8
通讯作者：
Yao, XB
中科院分区：
文献类型：
--
作者：
Cao, XW;Ding, X;Yao, XB
ERM（ezrin/radixin/moesin）蛋白在膜蛋白和皮质细胞骨架之间提供调节的连接，并且还参与信号转导途径。Ezrin定位于壁细胞的顶膜，并将蛋白激酶A激活级联反应偶联到胃壁细胞中调节的HCl分泌。在这里，我们表明，ezrin的完整性是必不可少的壁细胞激活，并提供了第一个证据，ezrin与PALS 1，一个进化保守的PDZ和SH 3结构域的蛋白质相互作用。我们的生物化学研究证实，ezrin结合PALS 1通过其N端，并与PALS 1共同定位于胃壁细胞的顶膜。此外，我们的研究表明，PALS 1是必不可少的埃兹蛋白的顶端定位，无论是抑制PALS 1蛋白的积累或删除PALS 1结合结构域埃兹蛋白消除了埃兹蛋白的顶端定位。最后，我们的研究表明ezrin-PALS 1相互作用在与壁细胞分泌相关的顶膜重塑中的重要作用。两者合计，这些结果定义了一种新的分子机制连接埃兹蛋白的保守的顶端极性复合物和极化上皮分泌的胃壁细胞中的作用。
The ERM (ezrin/radixin/moesin) proteins provide a regulated linkage between membrane proteins and the cortical cytoskeleton and also participate in signal transduction pathways. Ezrin is localized to the apical membrane of parietal cells and couples the protein kinase A activation cascade to regulated HCl secretion in gastric parietal cells. Here, we show that the integrity of ezrin is essential for parietal cell activation and provide the first evidence that ezrin interacts with PALS1, an evolutionarily conserved PDZ and SH3 domain-containing protein. Our biochemical study verifies that ezrin binds to PALS1 via its N terminus and is co-localized with PALS1 to the apical membrane of gastric parietal cells. Furthermore, our study shows that PALS1 is essential for the apical localization of ezrin, as either suppression of PALS1 protein accumulation or deletion of the PALS1-binding domain of ezrin eliminated the apical localization of ezrin. Finally, our study demonstrates the essential role of ezrin-PALS1 interaction in the apical membrane remodeling associated with parietal cell secretion. Taken together, these results define a novel molecular mechanism linking ezrin to the conserved apical polarity complexes and their roles in polarized epithelial secretion of gastric parietal cells.