The rat Na+-sulfate cotransporter rNaS2: functional characterization, tissue distribution, and gene (slc13a4) structure

• Published in: Pflügers Archiv Vol. 450; no. 4; pp. 262 - 268
• Main Authors: Dawson, Paul A, Pirlo, Katrina J, Steane, Sarah E, Nguyen, Kim A, Kunzelmann, Karl, Chien, Yu Ju, Markovich, Daniel
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01.07.2005
• Subjects: Animals; Base Sequence; Binding sites; Brain - metabolism; Female; Liver - metabolism; Molecular Sequence Data; Organic Anion Transporters, Sodium-Dependent - genetics; Organic Anion Transporters, Sodium-Dependent - physiology; Placenta - metabolism; Proteins; Rats; Reverse Transcriptase Polymerase Chain Reaction; Symporters - genetics; Symporters - physiology; Tissue Distribution
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-005-1414-6

Inorganic sulfate is essential for numerous functions in mammalian physiology. In the present study, we characterized the functional properties of the rat Na+-sulfate cotransporter NaS2 (rNaS2), determined its tissue distribution, and identified its gene (slc13a4) structure. Expression of rNaS2 protein in Xenopus oocytes led to a Na+-dependent transport of sulfate that was inhibited by phosphate, thiosulfate, tungstate, selenate, oxalate, and molybdate, but not by citrate, succinate, or DIDS. Transport kinetics of rNaS2 determined a K(M) for sulfate of 1.26 mM. Na+ kinetics determined a Hill coefficient of n=3.0+/-0.7, suggesting a Na+:SO4 (2-) stoichiometry of 3:1. rNaS2 mRNA was highly expressed in placenta, with lower levels found in the brain and liver. slc13a4 maps to rat chromosome 4 and contains 17 exons, spanning over 46 kb in length. This gene produces two alternatively spliced transcripts, of which the transcript lacking exon 2 is the most abundant form. Its 5' flanking region contains CAAT- and GC-box motifs and a number of putative transcription factor binding sites, including GATA-1, SP1, and AP-2 consensus sequences. This is the first study to characterize rNaS2 transport kinetics, define its tissue distribution, and resolve its gene (slc13a4) structure and 5' flanking region.