Cloning and characterization of a Na+-driven anion exchanger (NDAE1) - A new bicarbonate transporter

Regulation of intra- and extracellular ion activities (e,g. H+, Cl-, Na+) i s key to normal function of the central nervous system, digestive tract, re spiratory tract, and urinary system. With our cloning of an electrogenic Na +/HCO3- cotransporter (NBC), we found that NBC and the anion exchangers for m a bicarbonate transporter superfamily, Functionally three other HCO3- tra nsporters are known: a neutral Na+/HCO3- cotransporter, a K+/HCO3- cotransp orter, and a Na+-dependent Cl--HCO3- exchanger. We report the cloning and c haracterization of a Na+-coupled Cl--HCO3- exchanger and a physiologically unique bicarbonate transporter superfamily member. This Drosophila cDNA enc odes a 1030-amino acid membrane protein with both sequence homology and pre dicted topology similar to the anion exchangers and NBCs, The mRNA is expre ssed throughout Drosophila development and is prominent in the central nerv ous system. When expressed in Xenopus oocytes, this membrane protein mediat es the transport of Cl-, Na+, H+, and HCO3- but does not require HCO3-. Tra nsport is blocked by the stilbene 4,4'-diisothiocyanodihydrostilbene-2,2'-d isulfonates and may not be strictly electroneutral. Our functional data sug gest this Na+ driven anion exchanger (NDAE1) is responsible for the Nai-dep endent Cl--HCO3- exchange activity characterized in neurons, kidney, and fi broblasts. NDAE1 may be generally important for fly development, because di sruption of this gene is apparently lethal to the Drosophila larva.