Aquaporin-2 trafficking is regulated by PDZ-domain containing protein SPA-1
Aquaporin-2 trafficking is regulated by PDZ-domain containing protein SPA-1
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DOI：
10.1016/j.febslet.2004.05.021
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发表时间：
2004-06-18
期刊：
影响因子：
3.5
通讯作者：
Sasaki, S
中科院分区：
文献类型：
--
作者：
Noda, Y;Horikawa, S;Sasaki, S
水通道水通道蛋白2（AQP 2）的靶向定位严格调节体内水分稳态。AQP 2向顶膜的运输对于肾集合管中水的重吸收至关重要。控制AQP 2的顶端定位表明存在与AQP 2相互作用的蛋白质。对AQP 2相互作用蛋白的生物化学搜索导致鉴定出含有PDZ结构域的蛋白，信号诱导增殖相关基因-1（SPA-1），其是Rap 1的GTP酶激活蛋白（GAP）。SPA-1和AQP 2在肾集合管中的分布一致。共定位的网站是伴随着重新定位的水合状态。AQP 2运输到顶端膜被抑制SPA-1突变体缺乏Rap 1GAP活性和Rap 1的组成型活性突变体。SPA-1缺陷小鼠AQP 2运输受损。我们的研究结果表明，SPA-1直接结合到AQP 2和调节至少部分AQP 2的贩运。(C)2004年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Targeted positioning of water channel aquaporin-2 (AQP2) strictly regulates body water homeostasis. Trafficking of AQP2 to the apical membrane is critical to the reabsorption of water in renal collecting ducts. Controlled apical positioning of AQP2 suggests the existence of proteins that interact with AQP2. A biochemical search for AQP2-interacting proteins led to the identification of PDZ-domain containing protein, signal-induced proliferation-associated gene-1 (SPA-1) which is a GTPase-activating protein (GAP) for Rap1. The distribution of SPA-1 coincided with that of AQP2 in renal collecting ducts. The site of colocalization was concomitantly relocated by hydration status. AQP2 trafficking to the apical membrane was inhibited by the SPA-1 mutant lacking Rap1GAP activity and by the constitutively active mutant of Rap1. AQP2 trafficking was impaired in SPA-1-deficient mice. Our results show that SPA-1 directly binds to AQP2 and regulates at least in part AQP2 trafficking. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.