OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia.
The cellular and subcellular localization and mechanism of transport of the heteromeric organic solute transporter (OST) OSTalpha-OSTbeta was examined in human and rodent epithelia. The two subunits of the transporter were expressed together in human small intestine, kidney, and liver, tissues that also express the apical sodium-dependent bile acid uptake transporter ASBT (SLC10A2). Indirect immunofluorescence microscopy localized OSTalpha and OSTbeta to the basolateral membrane of mouse, rat, and human ileal enterocytes, renal proximal tubular cells, and cholangiocytes. Transport in OSTalpha-OSTbeta-expressing Xenopus laevis oocytes was unaffected by depletion of intracellular adenosine triphosphate, or by changes in transmembrane Na(+), K(+), H(+), or Cl(-) concentration gradients. However, the oocytes demonstrated robust substrate efflux and trans-stimulation, indicating that transport occurs by facilitated diffusion. Madin Darby canine kidney cells coexpressing mouse Ostalpha and Ostbeta exhibited enhanced apical to basolateral transport of the major glycine and taurine conjugated bile acid species. In conclusion, the selective localization of OSTalpha and OSTbeta to the basolateral plasma membrane of epithelial cells responsible for bile acid and sterol reabsorption, the substrate selectivity of the transporter, and the facilitated diffusion transport mode collectively indicate that OSTalpha-OSTbeta is a key basolateral transporter for the reabsorption of these important steroid-derived molecules.
Ballatori
Nazzareno
N
Department of Environmental Medicine, University of Rochester School of Medicine, NY 14642, USA. ned_ballatori@urmc.rochester.edu
Christian
Whitney V
WV
Lee
Jin Young
JY
Dawson
Paul A
PA
Soroka
Carol J
CJ
Boyer
James L
JL
Madejczyk
Michael S
MS
Li
Na
N
D000595:Amino Acid Sequence; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D004058:Diffusion; D004847:Epithelial Cells / Q000737:chemistry; D006801:Humans; D007422:Intestines / Q000737:chemistry*; D007668:Kidney / Q000737:chemistry*; D008099:Liver / Q000737:chemistry*; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013256:Steroids / Q000378:metabolism*
D001647:Bile Acids and Salts; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D013256:Steroids; C476575:organic solute transporter alpha, human; C476576:organic solute transporter alpha, mouse; C476577:SLC51B protein, human; C476578:organic solute transporter beta, mouse