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The different mode of organic anion transport in NPT1/ SLC17A1 and NPT4/ SLC17A3
Author(s) -
Jutabha Promsuk,
Endou Hitoshi,
Anzai Naohiko
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1099.1
Subject(s) - xenopus , pdz domain , transporter , chemistry , organic anion transporter 1 , organic anion , estrone sulfate , biophysics , voltage clamp , ion transporter , transport protein , kidney , biochemistry , microbiology and biotechnology , biology , ion , membrane potential , membrane , endocrinology , hormone , estrone , gene , organic chemistry
Voltage‐driven organic anion transporter has been hypothesized at the apical side of renal proximal tubule based on the classical membrane vesicle study. We first clarified its molecular identity (OATv1) in pig kidney, and searched its human ortholog. Human NPT1 ( SLC17A1 ) has the highest identity (63%) to amino acid sequence of pig OATv1, but does not mediate voltage‐driven transport. Recently, we identified NPT4 ( SLC17A3 ) as a human voltage‐driven organic anion transporter in kidney. To further clarify the difference of NPT1 and NPT4, we injected their cRNAs into Xenopus oocytes and compared transport properties. NPT1 showed broader substrate recognition for organic anions than NPT4. Estrone sulfate is a new substrate of NPT1 similar to NPT4. The major transport modes are different: Cl − exchange for NPT1 and voltage‐driven for NPT4. Both modes are observed in pig OATv1‐mediated transport. Deletion of PDZ‐motif at C‐terminus of NPT1, not in NPT4, abolished its transport function, suggesting that PDZ‐domain containing protein may regulate NPT1 function. The co‐localization of NPT1 and NPT4 at apical membrane of renal proximal tubules may be useful for the efficient organic anion secretion in kidney.