Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biochem J
2004 Mar 15;378Pt 3:949-57. doi: 10.1042/BJ20031261.
Show Gene links
Show Anatomy links
Functional features and genomic organization of mouse NaCT, a sodium-coupled transporter for tricarboxylic acid cycle intermediates.
Inoue K
,
Fei YJ
,
Zhuang L
,
Gopal E
,
Miyauchi S
,
Ganapathy V
.
???displayArticle.abstract???
In the present study, we report on the molecular cloning and functional characterization of mouse NaCT (Na+-coupled citrate transporter), the mouse orthologue of Drosophila Indy. Mouse NaCT consists of 572 amino acids and is highly similar to rat and human NaCTs in primary sequence. The mouse nact gene coding for the transporter is approx. 23 kb long and consists of 12 exons. When expressed in mammalian cells, the cloned transporter mediates the Na+-coupled transport of citrate and succinate. Competition experiments reveal that mouse NaCT also recognizes other tricarboxylic acid cycle intermediates such as malate, fumarate and 2-oxo-glutarate as excellent substrates. The Michaelis-Menten constant for the transport process is 38+/-5 mM for citrate and 37+/-6 mM for succinate at pH 7.5. The transport process is electrogenic and exhibits an obligatory requirement for Na+. Na+-activation kinetics indicates that multiple Na+ ions are involved in the activation process. Extracellular pH has a differential effect on the transport function of mouse NaCT depending on whether the transported substrate is citrate or succinate. The Michaelis-Menten constants for these substrates are also influenced markedly by pH. When examined in the Xenopus laevis oocyte expression system with the two-microelectrode voltage-clamp technique, the transport process mediated by mouse NaCT is electrogenic. The charge-to-substrate ratio is 1 for citrate and 2 for succinate. The most probable transport mechanism predicted by these studies involves the transport of citrate as a tervalent anion and succinate as a bivalent anion with a fixed Na+/substrate stoichiometry of 4:1. The present study provides the first unequivocal evidence for the electrogenic nature of mammalian NaCT.
Fei,
Preferential recognition of zwitterionic dipeptides as transportable substrates by the high-affinity peptide transporter PEPT2.
1999, Pubmed,
Xenbase
Fei,
Preferential recognition of zwitterionic dipeptides as transportable substrates by the high-affinity peptide transporter PEPT2.
1999,
Pubmed
,
Xenbase
Hatanaka,
Na+ - and Cl- -coupled active transport of nitric oxide synthase inhibitors via amino acid transport system B(0,+).
2001,
Pubmed
,
Xenbase
Helfand,
Regulation of gene expression during aging.
2000,
Pubmed
Helfand,
From genes to aging in Drosophila.
2003,
Pubmed
Inoue,
Functional identity of Drosophila melanogaster Indy as a cation-independent, electroneutral transporter for tricarboxylic acid-cycle intermediates.
2002,
Pubmed
,
Xenbase
Inoue,
Structure, function, and expression pattern of a novel sodium-coupled citrate transporter (NaCT) cloned from mammalian brain.
2002,
Pubmed
Inoue,
Human Na+ -coupled citrate transporter: primary structure, genomic organization, and transport function.
2002,
Pubmed
Inoue,
Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action.
2003,
Pubmed
Kekuda,
Primary structure and functional characteristics of a mammalian sodium-coupled high affinity dicarboxylate transporter.
1999,
Pubmed
Knauf,
Functional characterization and immunolocalization of the transporter encoded by the life-extending gene Indy.
2002,
Pubmed
,
Xenbase
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Nakanishi,
Na+- and Cl--coupled active transport of carnitine by the amino acid transporter ATB(0,+) from mouse colon expressed in HRPE cells and Xenopus oocytes.
2001,
Pubmed
,
Xenbase
Pajor,
Cloning and functional characterization of a high-affinity Na(+)/dicarboxylate cotransporter from mouse brain.
2001,
Pubmed
,
Xenbase
Pajor,
Sodium-coupled transporters for Krebs cycle intermediates.
1999,
Pubmed
,
Xenbase
Pajor,
Molecular cloning, chromosomal organization, and functional characterization of a sodium-dicarboxylate cotransporter from mouse kidney.
2000,
Pubmed
,
Xenbase
Pajor,
Molecular properties of sodium/dicarboxylate cotransporters.
2000,
Pubmed
Rogina,
Extended life-span conferred by cotransporter gene mutations in Drosophila.
2000,
Pubmed
Seth,
Mutations in novel organic cation transporter (OCTN2), an organic cation/carnitine transporter, with differential effects on the organic cation transport function and the carnitine transport function.
1999,
Pubmed
Sohal,
Oxidative stress, caloric restriction, and aging.
1996,
Pubmed
Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed
Wang,
Structure, function, and genomic organization of human Na(+)-dependent high-affinity dicarboxylate transporter.
2000,
Pubmed
,
Xenbase
