Routing of the aquaporin-2 water channel in health and disease

The identification OF the first water channel in 1991 opened up a new field in cell biology and physiology that significantly increased our understand ing of mammalian mater balance regulation. Since then, nine other mammalian aquaporins have been identified. Although the physiological significance o f many aquaporins is still to be elucidated, it has been clearly establishe d for aquaporin-2. This water channel, which is expressed in the renal coll ecting duct, is redistributed to the apical membrane in response to a intra cellular signaling cascade, initiated by binding of the antidiuretic hormon e vasopressin to its receptor. In pathological conditions, characterized by a reduced reabsorption of water from urine, the expression of aquaporin-2 and the apical targeting is always found to be reduced or absent. Naturally -occurring AQP2 mutations that cause Nephrogenic Diabetes Insipidus, a dise ase in which thtr kidney is unable to concentrate urine in response to vaso pressin, are extreme examples of this condition. In contrast, in diseases w ith increased renal water uptake, total and apical membrane expression of a quaporin-2 is increased. Since most aquaporins, including aquaporin-2, are considered to be constitutively open channels, much attention has been give n to the regulation of the shuttling of aquaporin-2 to the apical membrane. This review focusses on the present understanding of the regulation of the routing of aquaporin-2 in collecting duct cells and the misrouting of aqua porin-2 mutants in Nephrogenic Diabetes Insipidus.