Department of Biomedicine, Aarhus University and Center for Interactions of Proteins in Epithelial Transport, Aarhus University, Aarhus, Denmark.
Curr Opin Nephrol Hypertens. 2013 Sep;22(5):551-8. doi: 10.1097/MNH.0b013e328364000d.
Aquaporin-2 (AQP2) water channels in principal cells of the kidney collecting duct are essential for urine concentration. Due to application of modern technologies, progress in our understanding of AQP2 has accelerated in recent years. In this article, we highlight some of the new insights into AQP2 function that have developed recently, with particular focus on the cell biological aspects of AQP2 regulation.
AQP2 is subjected to a number of regulated modifications, including phosphorylation and ubiquitination, which are important for AQP2 function, cellular localization and degradation. AQP2 is likely internalized via clathrin and non-clathrin-mediated endocytosis. Regulation of AQP2 endocytosis, in addition to exocytosis, is a vital mechanism in determining overall AQP2 membrane abundance. AQP2 is associated with regulated membrane microdomains. Studies using membrane cholesterol depleting reagents, for example statins, have supported the role of membrane rafts in regulation of AQP2 trafficking. Noncanonical roles for AQP2, for example in epithelial cell migration, are emerging.
AQP2 function and thus urine concentration is dependent on a variety of cell signalling mechanisms, posttranslational modification and interplay between AQP2 and its lipid environment. This complexity of regulation allows fine-tuning of AQP2 function and thus body water homeostasis.
肾脏集合管主细胞中的水通道蛋白-2（AQP2）对于尿液浓缩至关重要。由于现代技术的应用，近年来我们对 AQP2 的理解取得了快速进展。在本文中，我们重点介绍了最近在 AQP2 功能方面的一些新见解，特别关注 AQP2 调节的细胞生物学方面。
AQP2 受到多种调节修饰，包括磷酸化和泛素化，这些修饰对 AQP2 的功能、细胞定位和降解都很重要。AQP2 可能通过网格蛋白和非网格蛋白介导的内吞作用被内化。AQP2 内吞作用的调节，除了外排作用，是决定整体 AQP2 膜丰度的重要机制。AQP2 与受调节的膜微区相关。使用膜胆固醇耗竭试剂（例如他汀类药物）的研究支持了质膜筏在 AQP2 运输调节中的作用。AQP2 的非典型作用，例如在上皮细胞迁移中的作用，正在出现。
AQP2 的功能，从而影响尿液浓缩，依赖于多种细胞信号机制、翻译后修饰以及 AQP2 与其脂质环境之间的相互作用。这种调节的复杂性允许 AQP2 功能的精细调节，从而维持身体的水稳态。
