β-Subunit of the Ostα-Ostβ Organic Solute Transporter Is Required Not Only for Heterodimerization and Trafficking but Also for Function

Abstract

Background: Deletion of Ost␣-Ost␤, an intestinal transporter that participates in the enterohepatic circulation of bile acids, lowers cholesterol and triglyceride levels. Results: Residues of Ost␤ required for interaction with Ost␣ and transport activity were identified. Conclusion: Distinct regions of Ost␤ are essential for Ost␣-Ost␤ trafficking and transport activity. Significance: Findings suggest strategies for inhibiting the holotransporter and reducing lipid levels.

The organic solute transporters alpha and beta are induced by hypoxia in human hepatocytes

“…. It has been shown that OSTβ is important for both the trafficking of OSTα to the plasma membrane as well as for its function . However, the lack of co‐immunoprecipitation of the mature, glycosylated form of OSTα upon immunoprecipitation of OSTβ suggests that the primary interaction may occur early in the biosynthetic pathway and may be transient .…”

Ostα−/−mice exhibit altered expression of intestinal lipid absorption genes, resistance to age-related weight gain, and modestly improved insulin sensitivity

“…After secretion into the intestinal lumen, bile acids are efficiently taken up into ileocytes via the ASBT; their subsequent efflux across the basolateral membrane, a requirement for return to the liver via the portal circulation, is mediated largely by OST␣-OST␤. OST consists of two subunits that heterodimerize for membrane delivery and generation of transport activity (2,4,15,31,33,37). OST␣-OST␤ was originally implicated in the basolateral efflux of bile acids in the ileum on the basis of its substrate specificity, tissue distribution, subcellular localization, and transcriptional regulation (2,5).…”

Characterization and treatment of persistent hepatocellular secretory failure

“…The organic solute transporter α‐β (OSTα‐OSTβ) is responsible for secretion of bile salts and conjugated steroids across the basolateral membrane of hepatocytes into the portal circulation . OSTβ is critically required for transport activity of the OSTα‐OSTβ heterodimer . The nuclear receptor FXR is considered the main regulator of OSTα and OSTβ expression .…”