Alternative splicing of the rat sodium/bile acid transporter changes its cellular localization and transport properties

Bile secretion involves the structural and functional interplay of hepatocy tes and cholangiocytes, the cells lining the intrahepatic bile ducts. Hepat ocytes actively secrete bile acids into the canalicular space and cholangio cytes then transport bile acids in a vectorial manner across their apical a nd basolateral plasma membranes. The initial step in the transepithelial tr ansport of bile acids across rat cholangiocytes is apical uptake by a Na+-d ependent bile acid transporter (ASBT). To date, the molecular basis of the obligate efflux mechanism for extrusion of bile acids across the cholangioc yte basolateral membrane remains unknown. We have identified an exon-2 skip ped, alternatively spliced form of ASBT, designated t-ASBT, expressed in ra t cholangiocytes, ileum, and kidney. Alternative splicing causes a frameshi ft that produces a 154-aa protein. Antipeptide antibodies detected the appr oximate to 19 kDa t-ASBT polypeptide in rat cholangiocytes, ileum, and kidn ey. The t-ASBT was specifically localized to the basolateral domain of chol angiocytes. Transport studies in Xenopus oocytes revealed that t-ASBT can f unction as a bile acid efflux protein. Thus, alternative splicing changes t he cellular targeting of ASBT, alters its functional properties, and provid es a mechanism for rat cholangiocytes and other bile acid-transporting epit helia to extrude bile acids. Our work represents an example in which a sing le gene appears to encode via alternative splicing both uptake and obligate efflux carriers in a bile acid-transporting epithelial cell.