MOLECULAR-CLONING OF A MERCURIAL-INSENSITIVE WATER CHANNEL EXPRESSED IN SELECTED WATER-TRANSPORTING TISSUES

Two mercurial-inhibitable water-transporting proteins have been identi fied: CHIP28, an erythrocyte water channel also expressed in kidney tu bules and selected extrarenal epithelia, and WCH-CD, a kidney collecti ng duct water channel. In searching for a protein responsible for the high transcellular water permeability in lung alveolus, we cloned a 32 -kDa water channel (mercurial-insensitive water channel (MIWC)) from a rat lung cDNA library with several novel features. Water permeability was strongly increased,in Xenopus oocytes expressing MIWC in a-mercur ial-insensitive manner, in contrast to known water channels. By in sit u hybridization, MIWC showed an unique distribution in cells that do n ot express CHIP28, including kidney papillary vasa recta, cells lining ther subarachnoid space and ventricles in brain, the inner nuclear la yer in retina, and the conjunctival epithelium. An alternatively splic ed form of MIWC with a 165-base pair deletion in the coding sequence w as also identified; relative expression of the spliced mRNA was tissue -specific. The MIWC water channel may participate in the urinary conce ntrating mechanism, the absorption of cerebrospinal fluid, and other p hysiological processes.