Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

References

  1. Crane, R. K., Miller, D. & Bihler, I. in Membrane Transport and Metabolism (eds Kleinzeller, A. & Kotyk, A.) 439–449 (Czech. Acad. Sci., Prague, 1961).

    Google Scholar 

  2. Wright, E. M., Hager, K. M. & Turk, E. Curr. Opin. Cell Biol. 4, 696–702 (1992).

    Article  CAS  Google Scholar 

  3. Ganapathy, V., Brandsch, M. & Leibach, F. H. Physiology of the Gastrointestinal Tract 3rd edn (ed. Johnson, L. R.) 1773–1794 (Raven, New York, 1994).

    Google Scholar 

  4. Tsay, Y.-F., Schroeder, J., Feldmann, K. A. & Crawford, N. M. Cell 72, 705–713 (1993).

    Article  CAS  Google Scholar 

  5. Perry, J. R., Basral, M. A., Steiner, H.-Y., Naider, F. & Becker, J. M. Molec. cell. Biol. 14, 104–115 (1994).

    Article  CAS  Google Scholar 

  6. Kaback, H. R. Biochim. biophys. Acta 1101, 210–213 (1992).

    CAS  PubMed  Google Scholar 

  7. Kanai, Y., Smith, C. P. & Hediger, M. A. FASEB. J. 7, 1450–1459 (1993).

    Article  CAS  Google Scholar 

  8. Truppathi, C., Ganapathy, V. & Leibach, F. H. J. biol. Chem. 265, 14870–14874 (1990).

    Google Scholar 

  9. Daniel, H. & Adibi, S. A. J. clin. Invest. 92, 2215–2223 (1993).

    Article  CAS  Google Scholar 

  10. Lombardo, Y. B., Morse, E. L. & Adibi, S. A. J. biol. Chem. 263, 12920–12926 (1988).

    CAS  PubMed  Google Scholar 

  11. Adedoyin, A., Perry, P. R. & Wilkinson, G. R. Drug Metab. Dispos. 21, 184–188 (1993).

    CAS  PubMed  Google Scholar 

  12. Adibi, A. A. & Mercer, D. W. J. clin. Invest. 52, 1586–1594 (1973).

    Article  CAS  Google Scholar 

  13. Ganapathy, V., Burckhardt, G. & Leibach, F. H. Biochim. biophys. Acta 816, 234–240 (1985).

    Article  CAS  Google Scholar 

  14. Dyer, J. et al. Biochim. J. 269, 565–571 (1990).

    Article  CAS  Google Scholar 

  15. Thwaites, D. T., Brown, C. D. A., Hirst, B. H. & Simmons, N. L. J. biol. Chem. 268, 7640–7642 (1993).

    CAS  PubMed  Google Scholar 

  16. Abe, M., Hoshi, T. & Tajima, A. J. Physiol. 394, 481–499 (1987).

    Article  CAS  Google Scholar 

  17. Kramer, W. et al. Eur. J. Biochem. 204, 923–930 (1992).

    Article  CAS  Google Scholar 

  18. Sinko, P. & Amidon, G. J. pharmac. Sci. 78, 723–727 (1989).

    Article  CAS  Google Scholar 

  19. Kanai, Y. & Hediger, M. A. Nature 360, 467–471 (1992).

    Article  ADS  CAS  Google Scholar 

  20. Lucas, M. Gut 24, 734–739 (1983).

    Article  CAS  Google Scholar 

  21. Ganapathy, V. & Leibach, F. H. J. biol. Chem. 258, 14189–14192 (1983).

    CAS  PubMed  Google Scholar 

  22. Siebens, A. W. & Boron, W. F. J. gen. Physiol. 90, 799–831 (1987).

    Article  CAS  Google Scholar 

  23. Davis, B. A., Hogan, E. M. & Boron, W. F. Am. J. Physiol. 263, C246–C256 (1992).

    Article  CAS  Google Scholar 

  24. Kanai, Y., Lee, W.-S., You, G., Brown, D. & Hediger, M. A. J. clin. Invest. 93, 397–404 (1994).

    Article  CAS  Google Scholar 

  25. You, G. et al. Nature 365, 844–847 (1993).

    Article  ADS  CAS  Google Scholar 

  26. Parent, L., Supplisson, S., Loo, D. D. F. & Wright, E. M. J. Membr. Biol. 125, 49–62 (1992).

    CAS  PubMed  Google Scholar 

  27. Mager, S. et al. Neuron 10, 177–188 (1993).

    Article  CAS  Google Scholar 

  28. Hediger, M. A., Coady, M. J., Ikeda, T. S. & Wright, E. M. Nature 330, 379–381 (1987).

    Article  ADS  CAS  Google Scholar 

  29. Hediger, M. A., Mendlein, J., Lee, H.-S. & Wright, E. M. Biochim. biophys. Acta 1064, 360–364 (1991).

    Article  CAS  Google Scholar 

  30. Wells, R. G. & Hediger, M. A. Proc. natn. Acad. Sci. U.S.A. 89, 5596–5600 (1992).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshikatsu Kanai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephan Nussberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vadivel Ganapathy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Frederick H. Leibach
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael F. Romero
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Satish K. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Walter F. Boron
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Matthias A. Hediger
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/368563a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing