CFTR chloride channel in the apical compartments: spatiotemporal coupling to its interacting partners.
CFTR chloride channel in the apical compartments: spatiotemporal coupling to its interacting partners.
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DOI：
10.1039/b924455g
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Naren AP
中科院分区：
文献类型：
--
作者：
Li C;Naren AP
囊性纤维化跨膜传导调节因子（CFTR）是一种cAMP调节的氯离子通道，主要位于气道、肠、胰腺、肾脏、汗腺以及男性生殖道上皮细胞的顶端或管腔表面，在跨上皮流体稳态中起关键作用。CFTR功能障碍可能是有害的，并可能导致危及生命的疾病。由于遗传缺陷导致的CFTR功能低下导致囊性纤维化，这是高加索人最常见的致命遗传疾病，而由各种感染引起的CFTR功能亢进引起分泌性腹泻，这是儿童早期死亡的主要原因。因此，维持CFTR上调过程和CFTR下调过程之间的动态平衡对于维持流体和身体内稳态至关重要。越来越多的证据表明，蛋白质-蛋白质相互作用在CFTR功能的微调调节中起着关键作用。越来越多的蛋白质被报道与CFTR氯离子通道直接或间接相互作用，这表明CFTR可能在空间和时间上与各种相互作用的伴侣偶联，包括离子通道、受体、转运蛋白、支架蛋白、酶分子、信号分子和效应物。大多数相互作用主要发生在CFTR蛋白的相对末端尾部（氨基或羧基）与其结合伴侣之间，直接或通过各种PDZ支架蛋白介导。这些动态相互作用影响通道功能，以及CFTR蛋白在细胞内的定位和加工。本文就CFTR与PDZ支架蛋白的相互作用，以及CFTR大分子信号复合物在分泌上皮极化细胞顶端区室的时空调控等方面的最新研究进展作一综述。
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel located primarily at the apical or luminal surfaces of epithelial cells in the airway, intestine, pancreas, kidney, sweat gland, as well as male reproductive tract, where it plays a crucial role in transepithelial fluid homeostasis. CFTR dysfunction can be detrimental and may result in life-threatening disorders. CFTR hypofunctioning because of genetic defects leads to cystic fibrosis, the most common lethal genetic disease in Caucasians, whereas CFTR hyperfunctioning resulting from various infections evokes secretory diarrhea, the leading cause of mortality in early childhood. Therefore, maintaining a dynamic balance between CFTR up-regulating processes and CFTR down-regulating processes is essential for maintaining fluid and body homeostasis. Accumulating evidence suggests that protein-protein interactions play a critical role in the fine-tuned regulation of CFTR function. A growing number of proteins have been reported to interact directly or indirectly with CFTR chloride channel, suggesting that CFTR might be coupled spatially and temporally to a wide variety of interacting partners including ion channels, receptors, transporters, scaffolding proteins, enzyme molecules, signaling molecules, and effectors. Most interactions occur primarily between the opposing terminal tails (amino or carboxyl) of CFTR protein and its binding partners, either directly or mediated through various PDZ scaffolding proteins. These dynamic interactions impact the channel function, as well as localization and processing of CFTR protein within cells. This article reviews the most recent progress and findings about the interactions between CFTR and its binding partners through PDZ scaffolding proteins, as well as the spatiotemporal regulation of CFTR-containing macromolecular signaling complexes in the apical compartments of polarized cells lining the secretory epithelia.
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