[Frontiers in Bioscience 14, 2829-2844, January 1, 2009]

OST alpha-OST beta: a key membrane transporter of bile acids and conjugated steroids

Nazzareno Ballatori1, Na Li1, Fang Fang1, James L. Boyer2, Whitney V. Christian1, Christine L. Hammond1

1Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, 2Department of Medicine and Liver Center, Yale University School of Medicine, New Haven, CT 06520

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Bile acid synthesis and disposition
4. Hepatic bile acid transporters
5. Intestinal bile acid transporters
6. Identification of Ost alpha-Ost beta
7. Ost alpha and Ost beta are expressed in most tissues, but are most abundant in tissues involved in bile acid and steroid homeostasis
8. Ost alpha-Ost beta mediates the transport of bile acids, conjugated steroids, and structurally-related molecules: transport occurs by a facilitated diffusion mechanism
9. Heterodimerization of Ost alpha and Ost beta increases the stability of the individual proteins, facilitates their post-translational modifications, and is required for delivery of the Ost alpha-Ost beta complex to the plasma membrane
10. Expression of both Ost genes is positively regulated by bile acids through the bile acid-activated farnesoid X receptor, Fxr
11. Ost alpha-Ost beta is required for bile acid and conjugated steroid disposition in the intestine, kidney, and liver
12. Implications for human diseases
13. Summary
14. Acknowledgements
15. References

1. ABSTRACT

The organic solute and steroid transporter, Ost alpha-Ost beta, is an unusual heteromeric carrier that appears to play a central role in the transport of bile acids, conjugated steroids, and structurally-related molecules across the basolateral membrane of many epithelial cells. The transporter's substrate specificity, transport mechanism, tissue distribution, subcellular localization, transcriptional regulation, as well as the phenotype of the recently characterized Ost alpha-deficient mice all strongly support this model. In particular, the Ost alpha-deficient mice display a marked defect in intestinal bile acid and conjugated steroid absorption; a decrease in bile acid pool size and serum bile acid levels; altered intestinal, hepatic and renal disposition of known substrates of the transporter; and altered serum triglyceride, cholesterol, and glucose levels. Collectively, the data indicate that Ost alpha-Ost beta is essential for bile acid and sterol disposition, and suggest that the carrier may be involved in human conditions related to imbalances in bile acid or lipid homeostasis.