An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton
An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton
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DOI：
10.1074/jbc.273.31.19797
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发表时间：
1998-07-31
影响因子：
4.8
通讯作者：
Milgram, SL
中科院分区：
文献类型：
--
作者：
Short, DB;Trotter, KW;Milgram, SL
囊性纤维化跨膜传导调节因子（CFTR）作为上皮细胞顶膜中的Cl-通道的功能被广泛记录。然而，知之甚少CFTR居住在顶端膜的分子决定因素，其Cl-通道活性的基础调节，以及其对其他转运蛋白功能的影响。CFTR功能的这些方面可能需要CFTR和上皮细胞顶室中的未知蛋白质之间的特异性相互作用。在这里，我们报告CFTR与最近发现的蛋白质EBP 50 GERM-binding phosphoprotein 50相互作用。在体内，EBP 50集中在人气道上皮细胞的顶膜处，并且CFTR和EBP 50在体外结合测定中缔合。CFTR-EBP 50相互作用需要CFTR的COOH末端DTRL序列，并利用EBP 50的PDZ 1或PDZ 2，尽管与PDZ 1的结合具有更大的亲和力。通过形成复合物，CFTR和EBP 50之间的相互作用可以影响细胞膜中CFTR Cl-通道功能的稳定性和/或调节，并提供CFTR可以影响其他顶端膜蛋白活性的潜在机制。
The function of the cystic fibrosis transmembrane conductance regulator (CFTR) as a Cl- channel in the apical membrane of epithelial cells is extensively documented. However, less is known about the molecular determinants of CFTR residence in the apical membrane, basal regulation of its Cl- channel activity, and its reported effects on the function of other transporters. These aspects of CFTR function likely require specific interactions between CFTR and unknown proteins in the apical compartment of epithelial cells. Here we report that CFTR interacts with the recently discovered protein, EBP50 GERM-binding phosphoprotein 50). EBP50 is concentrated at the apical membrane in human airway epithelial cells, in vivo, and CFTR and EBP50 associate in in vitro binding assays. The CFTR-EBP50 interaction requires the COOH-terminal DTRL sequence of CFTR and utilizes either PDZ1 or PDZ2 of EBP50, although binding to PDZ1 is of greater affinity. Through formation of a complex, the intel action between CFTR and EBP50 may influence the stability and/or regulation of CFTR Cl- channel function in the cell membrane and provides a potential mechanism through which CFTR can affect the activity of other apical membrane proteins.