Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2000 Sep 26;9720:11092-7. doi: 10.1073/pnas.200325297.
Show Gene links
Show Anatomy links
Alternative splicing of the rat sodium/bile acid transporter changes its cellular localization and transport properties.
Lazaridis KN
,
Tietz P
,
Wu T
,
Kip S
,
Dawson PA
,
LaRusso NF
.
???displayArticle.abstract???
Bile secretion involves the structural and functional interplay of hepatocytes and cholangiocytes, the cells lining the intrahepatic bile ducts. Hepatocytes actively secrete bile acids into the canalicular space and cholangiocytes then transport bile acids in a vectorial manner across their apical and basolateral plasma membranes. The initial step in the transepithelial transport of bile acids across rat cholangiocytes is apical uptake by a Na(+)-dependent bile acid transporter (ASBT). To date, the molecular basis of the obligate efflux mechanism for extrusion of bile acids across the cholangiocyte basolateral membrane remains unknown. We have identified an exon-2 skipped, alternatively spliced form of ASBT, designated t-ASBT, expressed in rat cholangiocytes, ileum, and kidney. Alternative splicing causes a frameshift that produces a 154-aa protein. Antipeptide antibodies detected the approximately 19 kDa t-ASBT polypeptide in rat cholangiocytes, ileum, and kidney. The t-ASBT was specifically localized to the basolateral domain of cholangiocytes. Transport studies in Xenopus oocytes revealed that t-ASBT can function as a bile acid efflux protein. Thus, alternative splicing changes the cellular targeting of ASBT, alters its functional properties, and provides a mechanism for rat cholangiocytes and other bile acid-transporting epithelia to extrude bile acids. Our work represents an example in which a single gene appears to encode via alternative splicing both uptake and obligate efflux carriers in a bile acid-transporting epithelial cell.
Alpini,
Functional expression of the apical Na+-dependent bile acid transporter in large but not small rat cholangiocytes.
1997, Pubmed
Alpini,
Functional expression of the apical Na+-dependent bile acid transporter in large but not small rat cholangiocytes.
1997,
Pubmed
Benedetti,
Carrier-mediated transport of conjugated bile acids across the basolateral membrane of biliary epithelial cells.
1997,
Pubmed
Christie,
Comparative analysis of the ontogeny of a sodium-dependent bile acid transporter in rat kidney and ileum.
1996,
Pubmed
Gerloff,
The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver.
1998,
Pubmed
,
Xenbase
Hallén,
Membrane insertion scanning of the human ileal sodium/bile acid co-transporter.
1999,
Pubmed
Hirano,
Characterization of the human apobec-1 gene: expression in gastrointestinal tissues determined by alternative splicing with production of a novel truncated peptide.
1997,
Pubmed
Hirohashi,
ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3 (Mrp3).
2000,
Pubmed
Jacquemin,
Expression of sodium-independent organic anion uptake systems of skate liver in Xenopus laevis oocytes.
1995,
Pubmed
,
Xenbase
Lazaridis,
Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium-dependent bile acid transporter.
1997,
Pubmed
Lee,
An alternatively spliced form of apobec-1 messenger RNA is overexpressed in human colon cancer.
1998,
Pubmed
McKeown,
Alternative mRNA splicing.
1992,
Pubmed
Nathanson,
Mechanisms and regulation of bile secretion.
1991,
Pubmed
Oelkers,
Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2).
1997,
Pubmed
Panayotova-Heiermann,
Five transmembrane helices form the sugar pathway through the Na+/glucose cotransporter.
1997,
Pubmed
,
Xenbase
Roberts,
The pathobiology of biliary epithelia.
1997,
Pubmed
Schölmerich,
Influence of hydroxylation and conjugation of bile salts on their membrane-damaging properties--studies on isolated hepatocytes and lipid membrane vesicles.
1984,
Pubmed
Shneider,
Cloning and molecular characterization of the ontogeny of a rat ileal sodium-dependent bile acid transporter.
1995,
Pubmed
Shneider,
Characterization of endogenous carrier-mediated taurocholate efflux from Xenopus laevis oocytes.
1993,
Pubmed
,
Xenbase
Sun,
Sorting of rat liver and ileal sodium-dependent bile acid transporters in polarized epithelial cells.
1998,
Pubmed
Tietz,
Isolation and characterization of rat cholangiocyte vesicles enriched in apical or basolateral plasma membrane domains.
1995,
Pubmed
Trauner,
Molecular pathogenesis of cholestasis.
1998,
Pubmed