title: Expression cloning of a mammalian proton-coupled oligopeptide transporter.
abstract: In mammals, active transport of organic solutes across plasma membranes was thought to be primarily driven by the Na+ gradient. Here we report the cloning and functional characterization of a H(+)-coupled transporter of oligopeptides and peptide-derived antibiotics from rabbit small intestine. This new protein, named PepT1, displays an unusually broad substrate specificity. PepT1-mediated uptake is electrogenic, independent of extracellular Na+, K+ and Cl-, and of membrane potential. PepT1 messenger RNA was found in intestine, kidney and liver and in small amounts in brain. In the intestine, the PepT1 pathway constitutes a major mechanism for absorption of the products of protein digestion. To our knowledge, the PepT1 primary structure is the first reported for a proton-coupled organic solute transporter in vertebrates and represents an interesting evolutionary link between prokaryotic H(+)-coupled and vertebrate Na(+)-coupled transporters of organic solutes.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Fei
authors.forename: Y
authors.initials: Y
authors.lastname: Kanai
authors.forename: S
authors.initials: S
authors.lastname: Nussberger
authors.forename: V
authors.initials: V
authors.lastname: Ganapathy
authors.forename: F H
authors.initials: FH
authors.lastname: Leibach
authors.forename: M F
authors.initials: MF
authors.lastname: Romero
authors.forename: S K
authors.initials: SK
authors.lastname: Singh
authors.forename: W F
authors.initials: WF
authors.lastname: Boron
authors.forename: M A
authors.initials: MA
authors.lastname: Hediger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D009865:Oocytes; D000074011:Peptide Transporter 1; D011487:Protein Conformation; D011817:Rabbits; D027981:Symporters; D014981:Xenopus
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D009842:Oligopeptides; D000074011:Peptide Transporter 1; D027981:Symporters