Molecular cloning and functional expression of a sodium-dicarboxylate cotransporter from human kidney

• Published in: The American journal of physiology Vol. 270; no. 4 Pt 2; pp. F642 - F648
• Main Author: Pajor, A M
• Format: Journal Article
• Language: English
• Published: United States 01-04-1996
• Subjects: Animals; Base Sequence; Carrier Proteins - genetics; Carrier Proteins - metabolism; Chromosome Mapping; Cloning, Molecular; Dicarboxylic Acid Transporters; Humans; Kidney - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Molecular Probes - genetics; Molecular Sequence Data; Organic Anion Transporters, Sodium-Dependent; Rabbits; Rats; Symporters; Tissue Distribution
• ISSN: 0002-9513
• DOI: 10.1152/ajprenal.1996.270.4.f642

The renal Na(+)-dicarboxylate cotransporter reabsorbs Krebs cycle intermediates, such as succinate and citrate, from the glomerular filtrate. The present study describes the cloning and characterization of the human renal Na(+)-dicarboxylate cotransporter, hNaDC-1. The amino acid sequence of hNaDC-1 is 78% identical to the rabbit renal Na(+)-dicarboxylate cotransporter, NaDC-1, and 42% identical to the rat renal Na(+)-sulfate transporter, NaSi-1. The carboxy terminus of hNaDC-1 protein contains two N-glycosylation sites that appear to be utilized. Xenopus oocytes injected with hNaDC-1 cRNA expressed a low-affinity Na(+)-dependent dicarboxylate transporter with Michaelis constant (Km) for succinate around 0.4 mM. The transport of succinate by hNaDC-1 was insensitive to the pH of the medium, whereas the transporter of citrate was stimulated by acidic pH. Northern blot analysis indicates that hNaDC-1 mRNA is found in both kidney and intestine. The gene for hNaDC-1 was localized to chromosome 17. This study provides the first demonstration that the human kidney contains a low-affinity Na(+)-dicarboxylate cotransporter with properties that resemble those of the Na(+)-dicarboxylate cotransporter on the apical membrane of the rabbit renal proximal tubule.