Molecular properties of the SLC13 family of dicarboxylate and sulfate transporters - PubMed (original) (raw)

Review

Molecular properties of the SLC13 family of dicarboxylate and sulfate transporters

Ana M Pajor. Pflugers Arch. 2006 Feb.

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.

PubMed Disclaimer

Figures

Fig. 1

Fig. 1

Secondary structure model of NaDC1 summarizing the results of cysteine scanning mutagenesis experiments. The rectangles represent the 11 transmembrane helices (TM). The protein has an intracellular N-terminus and an extracellular C-terminus containing the N-glycosylation site (shown by a Y) at Asn-578. Amino acids in TM 5–10 (shaded rectangles) and extracellular loop 5 (EL5) have been mutated to cysteines. The filled circles indicate the positions of substituted cysteines that are accessible to the methanethiosulfonate reagents, MTSET or MTSEA, at different conformational states of the protein. The results for TM 5 and 6 are based on studies with hNaS1 [41]. The results for the rest of the protein are from experiments done with rbNaDC1 [55, 59, 67]

References

    1. Artigas P, Gadsby DC. Na+/K+-pump ligands modulate gating of palytoxin-induced ion channels. Proc Natl Acad Sci USA. 2003;100:501–505. -PMC -PubMed
    1. Aruga S, Pajor AM, Nakamura K, Liu L, Moe OW, Preisig PA, Alpern RJ. OKP cells express the Na+-dicarboxylate cotransporter NaDC-1. Am J Physiol Cell Physiol. 2004;287:C64–C72. -PubMed
    1. Aruga S, Wehrli S, Kaissling B, Moe OW, Preisig PA, Pajor AM, Alpern RJ. Chronic metabolic acidosis increases NaDC-1 mRNA and protein abundance in rat kidney. Kidney Int. 2000;58:206–215. -PubMed
    1. Bai L, Pajor AM. Expression cloning of NaDC-2, an intestinal Na+- or Li+-dependent dicarboxylate transporter. Am J Physiol Gastrointest Liver. 1997;273:G267–G274. -PubMed
    1. Beck L, Markovich D. The mouse Na+-sulfate co-transporter gene Nas1. Cloning, tissue distribution, gene structure, chromosomal assignment, and transcriptional regulation by vitamin D. J Biol Chem. 2000;275:11880–11890. -PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources