Fenton Robert A, Murali Sathish K, Moeller Hanne B
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Am J Physiol Cell Physiol. 2020 Jul 1;319(1):C1-C10. doi: 10.1152/ajpcell.00150.2020. Epub 2020 May 20.
In mammals, conservation of body water is critical for survival and is dependent on the kidneys' ability to minimize water loss in the urine during periods of water deprivation. The collecting duct water channel aquaporin-2 (AQP2) plays an essential role in this homeostatic response by facilitating water reabsorption along osmotic gradients. The ability to increase the levels of AQP2 in the apical plasma membrane following an increase in plasma osmolality is a rate-limiting step in water reabsorption, a process that is tightly regulated by the antidiuretic hormone arginine vasopressin (AVP). In this review, the focus is on the role of the carboxyl-terminus of AQP2 as a key regulatory point for AQP2 trafficking. We provide an overview of AQP2 structure, disease-causing mutations in the AQP2 carboxyl-terminus, the role of posttranslational modifications such as phosphorylation and ubiquitylation in the tail domain, and their implications for balanced trafficking of AQP2. Finally, we discuss how various modifications of the AQP2 tail facilitate selective protein-protein interactions that modulate the AQP2 trafficking mechanism.
在哺乳动物中，保持体内水分对于生存至关重要，这依赖于肾脏在缺水期间将尿液中的水分流失降至最低的能力。集合管水通道蛋白2（AQP2）通过促进沿渗透梯度的水重吸收，在这种稳态反应中发挥着重要作用。血浆渗透压升高后，增加顶端质膜中AQP2水平的能力是水重吸收的限速步骤，这一过程受到抗利尿激素精氨酸加压素（AVP）的严格调控。在这篇综述中，重点是AQP2羧基末端作为AQP2转运关键调控点的作用。我们概述了AQP2的结构、AQP2羧基末端的致病突变、翻译后修饰（如尾部结构域中的磷酸化和泛素化）的作用及其对AQP2平衡转运的影响。最后，我们讨论了AQP2尾部的各种修饰如何促进选择性蛋白质-蛋白质相互作用，从而调节AQP2的转运机制。
