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Molecular Properties of the SLC13 Family of Dicarboxylate and Sulfate Transporters

Overview
Journal Pflugers Arch
Specialty Physiology
Date 2005 Oct 8
PMID 16211368
Citations 57
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Abstract

The SLC13 gene family consists of five members in humans, with corresponding orthologs from different vertebrate species. All five genes code for sodium-coupled transporters that are found on the plasma membrane. Two of the transporters, NaS1 and NaS2, carry substrates such as sulfate, selenate and thiosulfate. The other members of the family (NaDC1, NaDC3, and NaCT) are transporters for di- and tri-carboxylates including succinate, citrate and alpha-ketoglutarate. The SLC13 transporters from vertebrates are electrogenic and they produce inward currents in the presence of sodium and substrate. Substrate-independent leak currents have also been described. Structure-function studies have identified the carboxy terminal half of these proteins as the most important for determining function. Transmembrane helices 9 and 10 may form part of the substrate permeation pathway and participate in conformational changes during the transport cycle. This review also discusses new members of the SLC13 superfamily that exhibit both sodium-dependent and sodium-independent transport mechanisms. The Indy protein from Drosophila, involved in determining lifespan, and the plant vacuolar malate transporter are both sodium-independent dicarboxylate transporters, possibly acting as exchangers. The purpose of this review is to provide an update on new advances in this gene family, particularly on structure-function studies and new members of the family.

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References
1.
Inoue K, Fei Y, Huang W, Zhuang L, Chen Z, Ganapathy V . Functional identity of Drosophila melanogaster Indy as a cation-independent, electroneutral transporter for tricarboxylic acid-cycle intermediates. Biochem J. 2002; 367(Pt 2):313-9. PMC: 1222911. DOI: 10.1042/BJ20021132. View

2.
Inoue K, Zhuang L, Maddox D, Smith S, Ganapathy V . Structure, function, and expression pattern of a novel sodium-coupled citrate transporter (NaCT) cloned from mammalian brain. J Biol Chem. 2002; 277(42):39469-76. DOI: 10.1074/jbc.M207072200. View

3.
Burckhardt B, Drinkuth B, Menzel C, Konig A, Steffgen J, Wright S . The renal Na(+)-dependent dicarboxylate transporter, NaDC-3, translocates dimethyl- and disulfhydryl-compounds and contributes to renal heavy metal detoxification. J Am Soc Nephrol. 2002; 13(11):2628-38. DOI: 10.1097/01.asn.0000033463.58641.f9. View

4.
Knauf F, Rogina B, Jiang Z, Aronson P, Helfand S . Functional characterization and immunolocalization of the transporter encoded by the life-extending gene Indy. Proc Natl Acad Sci U S A. 2002; 99(22):14315-9. PMC: 137881. DOI: 10.1073/pnas.222531899. View

5.
Inoue K, Zhuang L, Ganapathy V . Human Na+ -coupled citrate transporter: primary structure, genomic organization, and transport function. Biochem Biophys Res Commun. 2002; 299(3):465-71. DOI: 10.1016/s0006-291x(02)02669-4. View