Type 1 Sodium-Dependent Phosphate Transporter acts as a Membrane Potential-Driven Urate Exporter
Takaaki Miyaji, Tatsuya Kawasaki, Natsuko Togawa, Hiroshi Omote and Yoshinori Moriyama
Affiliation: Advanced Science Research Center, Okayama University, Okayama 700-8530, Japan.
Keywords: Drug excretion, gout, membrane potential, Na+/inorganic phosphate transporter, non-steroidal anti-inflammatory
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.
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