Expression cloning of a mammalian proton-coupled oligopeptide transporter.
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.
Fei
Y J
YJ
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Kanai
Y
Y
Nussberger
S
S
Ganapathy
V
V
Leibach
F H
FH
Romero
M F
MF
Singh
S K
SK
Boron
W F
WF
Hediger
M A
MA
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
D002352:Carrier Proteins; D008565:Membrane Proteins; D009842:Oligopeptides; D000074011:Peptide Transporter 1; D027981:Symporters