Expression cloning of a mammalian proton-coupled oligopeptide transporter

• DOI: 10.1038/368563a0
• Publication Date: 2003-06-13T00:07:43Z
• Authors: You-Jun Fei; Yoshikatsu Kanai; Stephan Nussberger; Vadivel Ganapathy; Frederick H. Leibach; Michael F. Romero; Satish K. Singh; Walter F. Boron; Matthias A. Hediger
• Keywords: 0301 basic medicine; Symporters; Protein Conformation; Xenopus; Molecular Sequence Data; Membrane Proteins; Kidney; Peptide Transporter 1; Membrane Potentials; 03 medical and health sciences; Liver; Intestine, Small; Oocytes; Animals; Amino Acid Sequence; Rabbits; Cloning, Molecular; Carrier Proteins; Oligopeptides

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.