WATER TRANSPORT ACROSS MAMMALIAN-CELL MEMBRANES

This review summarizes recent progress in water-transporting mechanism s across cell membranes. Modern biophysical concepts of water transpor t and new measurement strategies are evaluated. A family of water-tran sporting proteins (water channels, aquaporins) has been identified, co nsisting of small hydrophobic proteins expressed widely in epithelial and nonepithelial tissues. The functional properties, genetics, and ce llular distributions of these proteins are summarized. The majority of molecular-level information about water-transporting mechanisms comes from studies on CHIP28, a 28-kDa glycoprotein that forms tetramers in membranes; each monomer contains six putative helical domains surroun ding a central aqueous pathway and functions independently as a water- selective channel. Only mutations in the vasopressin-sensitive water c hannel have been shown to cause human disease (non-X-linked congenital nephrogenic diabetes insipidus); the physiological significance of ot her water channels remains unproven. One mercurial-insensitive water c hannel has been identified, which has the unique feature of multiple o verlapping transcriptional units. Systems for expression of water chan nel proteins are described, including Xenopus oocytes, mammalian and i nsect cells, and bacteria. Further work should be directed at elucidat ion of the role of water channels in normal physiology and disease, mo lecular analysis of regulatory mechanisms, and water channel structure determination at atomic resolution.