EXPRESSION CLONING OF A MAMMALIAN PROTON-COUPLED OLIGOPEPTIDE TRANSPORTER

IN mammals, active transport of organic solutes across plasma membrane s was thought to be primarily driven by the Na+ gradient1-3. Here we r eport the cloning and functional characterization of a H+-coupled tran sporter of oligopeptides and peptide-derived antibiotics from rabbit s mall intestine. This new protein, named PepT1, displays an unusually b road substrate specificity. PepT1-mediated uptake is electrogenic, ind ependent of extracellular Na+, K+ and Cl-, and of membrane potential. PepT1 messenger RNA was found in intestine, kidney and liver and in sm all 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 f or a proton-coupled organic solute transporter in vertebrates and repr esents an interesting evolutionary link between prokaryotic H+-coupled and vertebrate Na+-coupled transporters of organic solutes.