Evolution of substrate specificity for the bile salt transporter ASBT (SLC10A2).

ABSTRACT: The apical Na(+)-dependent bile salt transporter (ASBT/SLC10A2) is essential for maintaining the enterohepatic circulation of bile salts. It is not known when Slc10a2 evolved as a bile salt transporter or how it adapted to substantial changes in bile salt structure during evolution. We characterized ASBT orthologs from two primitive vertebrates, the lamprey that utilizes early 5?-bile alcohols and the skate that utilizes structurally different 5?-bile alcohols, and compared substrate specificity with ASBT from humans who utilize modern 5?-bile acids. Everted gut sacs of skate but not the more primitive lamprey transported (3)H-taurocholic acid (TCA), a modern 5?-bile acid. However, molecular cloning identified ASBT orthologs from both species. Cell-based assays using recombinant ASBT/Asbt's indicate that lamprey Asbt has high affinity for 5?-bile alcohols, low affinity for 5?-bile alcohols, and lacks affinity for TCA, whereas skate Asbt showed high affinity for 5?- and 5?-bile alcohols but low affinity for TCA. In contrast, human ASBT demonstrated high affinity for all three bile salt types. These findings suggest that ASBT evolved from the earliest vertebrates by gaining affinity for modern bile salts while retaining affinity for older bile salts. Also, our results indicate that the bile salt enterohepatic circulation is conserved throughout vertebrate evolution.

SUBMITTER: Lionarons DA 

PROVIDER: S-EPMC3540847 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature