Targeting the collecting duct water channel aquaporin 2 (AQP2) to the plasma membrane is essential for the maintenance of mammalian water homeostasis. The vasopressin V2 receptor (V2R), which is a G_S protein-coupled receptor that increases intracellular cAMP levels, has a major role in this targeting process. Although a rise in cAMP levels and activation of protein kinase A are involved in facilitating the actions of V2R, studies in knockout mice and cell models have suggested that cAMP signalling pathways are not an absolute requirement for V2R-mediated AQP2 trafficking to the plasma membrane. In addition, although AQP2 phosphorylation is a known prerequisite for V2R-mediated plasma membrane targeting, none of the known AQP2 phosphorylation events appears to be rate-limiting in this process, which suggests the involvement of other factors; cytoskeletal remodelling has also been implicated. Notably, several regulatory processes and signalling pathways involved in AQP2 trafficking also have a role in the pathophysiology of autosomal dominant polycystic kidney disease, although the role of AQP2 in cyst progression is unknown. Here, we highlight advances in the field of AQP2 regulation that might be exploited for the treatment of water balance disorders and provide a rationale for targeting these pathways in autosomal dominant polycystic kidney disease.

将收集管水通道水通道蛋白 2 (AQP2) 靶向质膜对于维持哺乳动物水稳态至关重要。加压素 V2 受体 (V2R)，它是一种 G _S增加细胞内 cAMP 水平的蛋白偶联受体在该靶向过程中起主要作用。尽管 cAMP 水平的升高和蛋白激酶 A 的激活参与促进 V2R 的作用，但对基因敲除小鼠和细胞模型的研究表明，cAMP 信号通路并不是 V2R 介导的 AQP2 转运至质膜的绝对要求。此外，尽管 AQP2 磷酸化是 V2R 介导的质膜靶向的已知先决条件，但已知的 AQP2 磷酸化事件似乎都不是该过程中的限速事件，这表明其他因素的参与；细胞骨架重塑也有牵连。尤其，尽管 AQP2 在囊肿进展中的作用尚不清楚，但参与 AQP2 运输的几个调节过程和信号通路也在常染色体显性多囊肾病的病理生理学中发挥作用。在这里，我们重点介绍了 AQP2 调节领域的进展，这些进展可用于治疗水平衡障碍，并为在常染色体显性多囊肾病中靶向这些通路提供了理论依据。