Butterworth Michael B
Department Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Biochim Biophys Acta. 2010 Dec;1802(12):1166-77. doi: 10.1016/j.bbadis.2010.03.010. Epub 2010 Mar 27.
The epithelial Na(+) channel (ENaC) is a major regulator of salt and water reabsorption in a number of epithelial tissues. Abnormalities in ENaC function have been directly linked to several human disease states including Liddle syndrome, psuedohypoaldosteronism, and cystic fibrosis and may be implicated in salt-sensitive hypertension. ENaC activity in epithelial cells is regulated both by open probability and channel number. This review focuses on the regulation of ENaC in the cells of the kidney cortical collecting duct by trafficking and recycling. The trafficking of ENaC is discussed in the broader context of epithelial cell vesicle trafficking. Well-characterized pathways and protein interactions elucidated using epithelial model cells are discussed, and the known overlap with ENaC regulation is highlighted. In following the life of ENaC in CCD epithelial cells the apical delivery, internalization, recycling, and destruction of the channel will be discussed. While a number of pathways presented still need to be linked to ENaC regulation and many details of the regulation of ENaC trafficking remain to be elucidated, knowledge of these mechanisms may provide further insights into ENaC activity in normal and disease states.
上皮钠离子通道（ENaC）是多种上皮组织中盐和水重吸收的主要调节因子。ENaC功能异常与多种人类疾病状态直接相关，包括利德尔综合征、假性醛固酮增多症和囊性纤维化，并且可能与盐敏感性高血压有关。上皮细胞中的ENaC活性受开放概率和通道数量的调节。本综述聚焦于通过转运和再循环对肾皮质集合管细胞中ENaC的调节。ENaC的转运在更广泛的上皮细胞囊泡转运背景下进行讨论。讨论了使用上皮模型细胞阐明的特征明确的途径和蛋白质相互作用，并突出了与ENaC调节的已知重叠部分。在追踪ENaC在集合管上皮细胞中的生命历程时，将讨论该通道的顶端递送、内化、再循环和降解。虽然所呈现的许多途径仍需与ENaC调节相联系，并且ENaC转运调节的许多细节仍有待阐明，但对这些机制的了解可能会为正常和疾病状态下的ENaC活性提供进一步的见解。
