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Expression cloning of a mammalian proton-coupled oligopeptide transporter

Nature volume 368, pages 563–566 (1994)Cite this article

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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Author notes

  1. Yoshikatsu Kanai

    Present address: Department of Pharmacology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181, Japan

Authors and Affiliations

  1. Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 75 Francis Street, Boston, Massachusetts, 02115, USA

    You-Jun Fei, Yoshikatsu Kanai, Stephan Nussberger & Matthias A. Hediger

  2. Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia, 30912, USA

    You-Jun Fei, Vadivel Ganapathy & Frederick H. Leibach

  3. Department of Cellular and Molecular Physiology, Yale University, School of Medicine, 333 Cedar Street, New Haven, Connecticut, 06510, USA

    Michael F. Romero, Satish K. Singh & Walter F. Boron

Authors
  1. You-Jun Fei
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  2. Yoshikatsu Kanai
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  4. Vadivel Ganapathy
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  5. Frederick H. Leibach
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  9. Matthias A. Hediger
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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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