The role of renal water channels in health and disease

Abstract

Seven members of the aquaporin (AQP) family are expressed in different regions of the kidney. AQP1-4 are localized in plasma membranes of renal epithelial cells and are intimately involved in water reabsorption by the kidney. AQP7 is also localized in the plasma membrane and may facilitate glycerol transport. AQP6 and AQP11 are localized within the cell, with AQP6 involved in anion transport and AQP11 water transport. Mutations in AQP2 can result in diabetes insipidus, whereas mutations in other AQPs have not yet been shown to be disease-associated. Genetic polymorphisms may contribute to the susceptibility to defects in urine concentrating mechanisms associated with some diseases. Most of the AQPs are subject to transcriptional regulation and post-translational modifications by a range of biological modifiers. As a result a number of chronic kidney and systemic diseases produce changes in the abundance of AQPs. The more recent developments in this field are reviewed.

Fig. 1.

AQP2 trafficking in principal cells This model depicts how the interaction of PGE₂ or vasopressin (VP) with either the PGE₂ receptor (EP₃) or the vasopressin receptor (V2R) in the basolateral membrane of a principal cell results in the incorporation of AQP2 (blue ovals) into the apical membrane. The phosphorylation of AQP2 by protein kinase A (PKA) signals its translocation from an intracellular vesicle to the plasma membrane. Steps that regulate this process are shown and revolve around guanylate cyclase (GC), adenylate cyclase (AC) and calcium (Ca²⁺). Taken with permission from Bouley et al. (2008).