Physiology and pathophysiology of water transport: The role of aquaporins

The recent molecular cloning of a group of water-transporting proteins, the aquaporins, has greatly contributed to the understanding of water transport physiology and pathophysiology. So far, six mammalian aquaporins have been identified, four of which are expressed in the kidney. The oldest of these six channel proteins, the major intrinsic protein (MIP) of lens, renamed aquaporin-0, has only recently joined the aquaporin family since initially it was not known to be a water-transporter. Aberrant expression of the aquaporin-0 gene has been demonstrated in mice with congenital cataract, Aquaporin-1, abundantly present in proximal nephron and descending Henle limbs, seems largely responsible for renal fluid reabsorption, Surprisingly, however, individuals who are homozygous for an aquaporin-1 mutation appeared to be healthy, Aquaporin-2 is the water channel which is inserted into the apical membrane of renal collecting duct cells in response to the antidiuretic hormone arginine vasopressin, In some patients with congenital nephrogenic diabetes insipidus, defects in the aquaporin-2 gene have been found, whereas a decrease in aquaporin-2 gene expression has been observed in patients with acquired nephrogenic diabetes insipidus, Natural mutants of aquaporin-3, -4 and -5 have not been reported, Aquaporin-3 and -4 water channels are thought to be involved in fluid transport across the basolateral membrane of collecting duct cells, In terms of clinical significance, the abundance and putative functions of aquaporin-4 in the brain are especially intriguing, Aquaporin-5 has not been detected in the kidney, but seems to play a role in the secretion of saliva, tears and pulmonary fluid.