Type 1 Sodium-Dependent Phosphate Transporter acts as a Membrane Potential-Driven Urate Exporter

Takaaki      Miyaji; Tatsuya      Kawasaki; Natsuko      Togawa; Hiroshi      Omote; Yoshinori      Moriyama

Abstract

SLC17A1 protein (NPT1) was the first identified member of the SLC17 phosphate transporter family, and is known to mediate Na⁺/inorganic phosphate (Pi) co-transport when expressed in Xenopus oocytes. Although this protein was suggested to be a renal polyspecific anion exporter, its transport properties were not well characterized. The clean biochemical approach revealed that proteoliposomes comprising purified NPT1 as the only protein source transport various organic anions such as urate, p-aminohippuric acid (PAH), and acetylsalicylic acid (aspirin) in a membrane potential (Δψ)-driven and Cl^- -dependent manner. Human NPT1 carrying an SNP mutation, Thr269Ile, known to increase the risk of gout, exhibited 32% lower urate transport activity compared to the wild type protein, leading to the conclusion that NPT1 is the long searched for transporter responsible for renal urate excretion. In the present article, we summarized the history of identification of the urate exporter and its possible involvement in the dynamism of urate under physiological and pathological conditions.

Keywords: Drug excretion, gout, membrane potential, Na⁺/inorganic phosphate transporter, non-steroidal anti-inflammatory drug, urate.