Molecular cloning and functional expression of a sodium/
dicarboxylate cotransporter from human kidney.
Pajor, Ana M.
University of Arizona, Department of Physiology, College of
Medicine, Tucson, AZ 85724
APStracts 2:0194F, 1995.
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, sodium-dependent dicarboxylate
transporter with Km for succinate around 0.4 mM. The transport of
succinate by hNaDC-1 was insensitive to the pH of the medium, while
the transport 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.
Received 5 July 1995; accepted in final form 20 October 1995.
APS Manuscript Number F211-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95