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 understanding of mammalian water balance regulation. Since then, nine other mammalian aquaporins have been identified. Although the physiological significance of many aquaporins is still to be elucidated, it has been clearly established for aquaporin-2. This water channel, which is expressed in the renal collecting duct, is redistributed to the apical membrane in response to a intracellular signaling cascade, initiated by binding of the antidiuretic hormone 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 disease in which the kidney is unable to concentrate urine in response to vasopressin, are extreme examples of this condition. In contrast, in diseases with increased renal water uptake, total and apical membrane expression of aquaporin-2 is increased. Since most aquaporins, including aquaporin-2, are considered to be constitutively open channels, much attention has been given 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 aquaporin-2 mutants in Nephrogenic Diabetes Insipidus.
Deen
P M
PM
Department of Cell Physiology, University of Nijmegen, The Netherlands. peterd@sci.kun.nl
van Balkom
B W
BW
Kamsteeg
E J
EJ
D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000378:metabolism; D002451:Cell Compartmentation / Q000235:genetics; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007022:Hypotension / Q000150:complications / Q000209:etiology; D007685:Kidney Tubules, Collecting / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation / Q000502:physiology; D021381:Protein Transport / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*; D014882:Water-Electrolyte Balance / Q000502:physiology*
C496023:AQP2 protein, human; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D001127:Arginine Vasopressin