SEQUENCE AND FUNCTIONAL-CHARACTERIZATION OF A RENAL SODIUM DICARBOXYLATE COTRANSPORTER

The cDNA coding for a rabbit renal Na+/dicarboxylate cotransporter, de signated NaDC-1, was isolated by functional expression in Xenopus oocy tes, NaDC-1 cDNA is approximately 2.3 kilobases in length and codes fo r a protein of 593 amino acids, NaDC-1 protein contains eight putative transmembrane domains, and the sequence and secondary structure are r elated to the renal Na+/sulfate transporter, NaSi-1. Northern analysis shows that the NdDC-1 message is abundant in kidney and small intesti ne, and related transporters may be found in liver, lung, and adrenal. The transport of succinate by NaDC-1 was sodium-dependent, sensitive to inhibition by lithium, and inhibited by a range of di- and tricarbo xylic acids, This transporter also carries citrate, but it does not tr ansport lactate, In kinetic experiments, the K-m for succinate was aro und 0.4 mM and the V-max was 15 nmol/oocyte/h, while the Hill coeffici ent of Na+ activation of succinate transport was 1.9. The transport of succinate by NaDC-1 was insensitive to changes in pH, whereas the tra nsport of citrate increased with decreasing pH, in parallel with the c oncentration of divalent citrate in the medium, The results of the fun ctional characterization indicate that NaDC-1 likely corresponds to th e renal brush-border Na+/dicarboxylate cotransporter.