Molecular biology of multispecific organic anion transporter family (OAT family)

Abstract

It has been predicted that a variety of organic anions of endogenous and exogenous origin are secreted by the renal proximal tubules via the p-aminohippurate (PAH) transport system. Organic anions are taken up from the peritubular plasma by the basolateral PAH transporter, and subsequently excreted into the urine by distinct organic anion transporter(s) in the luminal membrane. In 1997, we isolated the PAH transporter, organic anion transporter 1 (OAT1), from the rat kidney by the expression cloning method. OAT1 is a 551-amino-acid residue protein with 12 putative membrane spanning domains. It is exclusively expressed in the kidney, and is localized to the basolateral membrane of the cells of the middle portion of the proximal tubule, S2. OAT1 is a sodium-independent, organic anion/dicarboxylateexchanger, and mediates the transport of various organic anions. We have also identified two other isoforms of OAT. Rat OAT2 is predominantly expressed in the liver, while rat OAT3 is expressed in the liver, kidney, brain, and eyes. The isoforms exhibit overlapping but distinct substrate specificities. Interestingly, the members of the OAT family are structurally related to the members of the organic cation transporter (OCT) family. In addition, we have identified a membrane protein showing homology to both OATs and OCTs. This clone (CT1) mediated the transport of carnitine, a zwitterion. In this article, we describe the structure and functions of the members of the OAT family in association with these features in members of the OCT family and the zwitterion transporter.