Structure of renal organic anion and cation transporters

• Published in: American journal of physiology. Renal physiology 2000-06, Vol.278 (6), p.F853-F866
• Main Authors: Burckhardt, G, Wolff, N A
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Anion Transport Proteins; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Humans; Ion Transport; Kidney - metabolism; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Models, Molecular; Molecular Sequence Data; Rats; Sequence Homology, Amino Acid; Tissue Distribution
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.2000.278.6.f853

Here we review the structural and functional properties of organic anion transporters (OAT1, OAT2, OAT3) and organic cation transporters (OCTN1, OCTN2, OCT1, OCT2, OCT3), some of which are involved in renal proximal tubular organic anion and cation secretion. These transporters share a predicted 12-transmembrane domain (TMD) structure with a large extracellular loop between TMD1 and TMD2, carrying potential N-glycosylation sites. Conserved amino acid motifs revealed a relationship to the sugar transporter family within the major facilitator superfamily. Following heterologous expression, most OATs transported the model anion p-aminohippurate (PAH). OAT1, but not OAT2, exhibited PAH-alpha-ketoglutarate exchange. OCT1-3 transported the model cations tetraethylammonium (TEA), N(1)-methylnicotinamide, and 1-methyl-4-phenylpyridinium. OCTNs exhibited transport of TEA and/or preferably the zwitterionic carnitine. Substrate substitution as well as cis-inhibition experiments demonstrated polyspecificity of the OATs, OCTs, and OCTN1. On the basis of comparison of the structurally closely related OATs and OCTs, it may be possible to delineate the binding sites for organic anions and cations in future experiments.