Biology of a novel organic solute and steroid transporter, OSTα-OSTβ

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 alpha) and a putative 128-amino acid, single-TM domain ancillary polypeptide (OST beta). When OST alpha and OST beta are coexpressed in Xenopus oocytes, they are able to mediate transport of estrone 3-sulfate, dehydroepiandrosterone 3-sulfate, taurocholate, digoxin, and prostaglandin E-2, indicating a role in the disposition of key cellular metabolites or signaling molecules. OST alpha and OST beta 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 alpha and OST beta proteins are localized to the basolateral membrane of mouse enterocytes. In MDCK cells, mouse Ost alpha-Ost beta 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 alpha-OST beta 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.