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-OSTß
Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York 14642; and the Mount Desert Island Biological Laboratory, Salsbury Cove, Maine 04672
To whom requests for reprints should be addressed at 1 Department of Environmental Medicine, Box EHSC, University of Rochester School of Medicine, 575 Elmwood Avenue, Rochester, NY 14642. E-mail: Ned_Ballatori{at}urmc.rochester.edu
Using a comparative approach, recent studies have identified and functionally characterized a new type of organic solute and steroid transporter (OST) from skate, mouse, rat, and human genomes. In contrast to all other organic anion transporters identified to date, transport activity requires the coexpression of two distinct gene products, a predicted 340–amino acid, seven-transmembrane (TM) domain protein (OST
) and a putative 128–amino acid, single-TM domain ancillary polypeptide (OSTß). When OST and OSTß are coexpressed in Xenopus oocytes, they are able to mediate transport of estrone 3-sulfate, dehydroepiandrosterone 3- sulfate, taurocholate, digoxin, and prostaglandin E2, indicating a role in the disposition of key cellular metabolites or signaling molecules. OST and OSTß are expressed at relatively high levels in intestine, kidney, and liver, but they are also expressed at lower levels in many human tissues. Indirect immunofluorescence microscopy revealed that intestinal OST and OSTß proteins are localized to the baso-lateral membrane of mouse enterocytes. In MDCK cells, mouse Ost–Ostß mediated the vectorial movement of taurocholate from the apical to the basolateral membrane, but not in the opposite direction, indicating basolateral efflux of bile acids. Overall, these findings indicate that OST-OSTß is a heteromeric transporter that is localized to the basolateral membrane of specific epithelial tissues and serves to regulate the export and disposition of bile acids and structurally related compounds from the cell. If confirmed, this model would have important implications for the body’s handling of various steroid-derived molecules and may provide a new pharmacologic target for altering sterol homeostasis.
Key Words: steroid transporter • organic solute transporter • basolateral membrane • bile acid reabsorption
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