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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+ gradient1–3. 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.

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Fei, YJ., Kanai, Y., Nussberger, S. et al. Expression cloning of a mammalian proton-coupled oligopeptide transporter. Nature 368, 563–566 (1994). https://doi.org/10.1038/368563a0

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