Molecular cloning and functional expression of a sodium-dicarboxylate cotransporter from human kidney.
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.
Pajor
A M
AM
University of Arizona, Department of Physiology, College of Medicine, Tucson 85724, USA.
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D029382:Dicarboxylic Acid Transporters; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D029363:Organic Anion Transporters, Sodium-Dependent; D011817:Rabbits; D051381:Rats; D027981:Symporters; D014018:Tissue Distribution
D002352:Carrier Proteins; D029382:Dicarboxylic Acid Transporters; D008565:Membrane Proteins; D015335:Molecular Probes; D029363:Organic Anion Transporters, Sodium-Dependent; C092524:SLC13A2 protein, human; C490478:Slc13a2 protein, rat; D027981:Symporters