Phosphorylation of human AQP2 and its role in trafficking.

Human Aquaporin 2 (AQP2) is a membrane-bound water channel found in the kidney collecting duct whose regulation by trafficking plays a key role in regulating urine volume. AQP2 trafficking is tightly controlled by the pituitary hormone arginine vasopressin (AVP), which stimulates translocation of AQP2 residing in storage vesicles to the apical membrane. The AVP-dependent translocation of AQP2 to and from the apical membrane is controlled by multiple phosphorylation sites in the AQP2 C-terminus, the phosphorylation of which alters its affinity to proteins within the cellular membrane protein trafficking machinery. The aim of this chapter is to provide a summary of what is currently known about AVP-mediated AQP2 trafficking, dissecting the roles of individual phosphorylation sites, kinases and phosphatases and interacting proteins. From this, the picture of an immensely complex process emerges, of which many structural and molecular details remains to be elucidated.