Aquaporins and the Kidney

The discovery of aquaporins--the protein family of water channels which regulate water transport in the kidney and many other tissues--was considered significant enough to win the Nobel Prize in Chemistry for Peter Agre in 2003.  

The aquaporins are a large family--there are at least 12 aquaporin genes in humans and possibly more--but which ones are important in the kidney?  It turns out that different aquaporins are expressed in discrete segments along the nephron.  The one which gets the most attention is likely aquaporin-2 (AQP2), which is expressed in the apical membrane and intracellular vesicles of principal cells of the collecting duct.  AQP2 is the predominant vasopressin-responsive aquaporin, and is therefore responsible for the majority of regulation of water reabsorption in the collecting duct.  According to the current model, vasopressin binds to its receptor on the basolateral surface of collecting duct cells, resulting in an increase in cyclic AMP, protein kinase A activity, and the increased trafficking of intracellular AQP2-containing vesicles to the apical membrane, where they fuse with the plasma membrane and allow water reabsorption to take place.  Mutations in the AQP2 gene account for some cases of nephrogenic diabetes insipidus. 

 

The other aquaporins also play specific roles in water transport.  For instance, aquaporins-3 and -4 are expressed at the basolateral surface of cortical collecting duct cells and are responsible for movement of water taken in by AQP2.  Aquaporin-1 is extremely abundant in the proximal convoluted tubule and descending thin limb, but is notably absent in highly water-impermeable segments such as the ascending thin limb, thick ascending limb, and distal tubule.