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^1-3. 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 PepTl 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.