Type 1 sodium-dependent phosphate transporter (SLC17A1 protein) is a Cl--dependent urate exporter

Masafumi Iharada, Takaaki Miyaji, Takahiro Fujimoto, Miki Hiasa, Naohiko Anzai, Hiroshi Omote, Yoshinori Moriyama

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

SLC17A1 protein (NPT1) is the first identified member of the SLC17 phosphate transporter family and mediates the transmembrane cotransport of Na+/Pi in oocytes. Although this protein is believed to be a renal polyspecific anion exporter, its transport properties are not well characterized. Here, we show that proteoliposomes containing purified SLC17A1 transport various organic anions such as p-aminohippuric acid and acetyl-salicylic acid (aspirin) in an inside positive membrane potential (Δψ)-dependent manner. We found that NPT1 also transported urate. The uptake characteristics were similar to that of SLC17 members in its Cl - dependence and inhibitor sensitivity. When arginine 138, an essential amino acid residue for members of the SLC17 family such as the vesicular glutamate transporter, was specifically mutated to alanine, the resulting mutant protein was inactive in Δψ-dependent anion transport. Heterologously expressed and purified human NPT1 carrying the single nucleotide polymorphism mutation that is associated with increased risk of gout in humans exhibited 32% lower urate transport activity compared with the wild type protein. These results strongly suggested that NPT1 is a Cl-- dependent polyspecific anion exporter involved in urate excretion under physiological conditions.

Original languageEnglish
Pages (from-to)26107-26113
Number of pages7
JournalJournal of Biological Chemistry
Volume285
Issue number34
DOIs
Publication statusPublished - Aug 20 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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