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.

Primary structure and functional characterization of a high-affinity glutamate transporter

Abstract

GLUTAMATE transport across plasma membranes of neurons, glial cells and epithelial cells of the small intestine and kidney proceeds by high- and low-affinity transport systems1–5. High-affinity (Km 2–50 μM) transport systems have been described1,6,7 that are dependent on Na+ but not Cl ions and have a preference for L-glutamate and D- and L-aspartate. In neurons high-affinity glutamate transporters are essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft6,7. We have isolated a complementary DNA encoding an electrogenic Na+ but not Cl-dependent high-affinity glutamate transporter (named EAAC1) from rabbit small intestine by expression in Xenopus oocytes. We find EAAC1 transcripts in specific neuronal structures in the central nervous system as well as in the small intestine, kidney, liver and heart. The function and pharmacology of the expressed protein are characteristic of the high-affinity glutamate transporter already identified in neuronal tissues. The abnormal glutamate transport that is associated with certain neurodegenerative diseases8 and which occurs during ischaemia and anoxia7 could be due to abnormalities in the function of this protein.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. Schousboe, A. Int. Rev. Neurobiol. 22, 1–45 (1981).

    Article  CAS  Google Scholar 

  2. Kanner, B. I. & Schuldiner, S. CRC Crit. Rev. Biochem. 22, 1–38 (1987).

    Article  CAS  Google Scholar 

  3. Christensen, H. N. Physiol. Rev. 70, 43–77 (1990).

    Article  CAS  Google Scholar 

  4. Wingrove, T. G. & Kimmich, G. A. Am. J. Physiol. 255, C737–744 (1988).

    Article  CAS  Google Scholar 

  5. Silbernagl, S. Klin. Wochenschr. 57, 1009–1019 (1979).

    Article  CAS  Google Scholar 

  6. Fonnum, F. J. Neurochem. 42, 1–11 (1984).

    Article  CAS  Google Scholar 

  7. Nicholls, D. & Attwell, D. Trends pharmac. Sci. 11, 462–468 (1990).

    Article  Google Scholar 

  8. Rothstein, J. D., Martin, L. J. & Kuncl, R. W. New Engl. J. Med. 326, 1464–1468 (1992).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  10. Eisenberg, D., Schwarz, E., Komaromy, M. & Wall, R. J. molec. Biol. 179, 125–142 (1984).

    Article  CAS  Google Scholar 

  11. Wang, C.-D., Buck, M. A. & Fraser, C. M. Molec. Pharmac. 40, 168–179 (1991).

    CAS  Google Scholar 

  12. Ferkaney, J. & Coyle, J. T. J. Neurosci. Res. 16, 491–503 (1986).

    Article  Google Scholar 

  13. Brew, H. & Attwell, D. Nature 327, 707–709 (1987).

    Article  ADS  CAS  Google Scholar 

  14. Cox, D. W., Headley, M. H. & Watkins, J. C. J. Neurochem. 29, 579–588 (1977).

    Article  CAS  Google Scholar 

  15. Robinson, M. B., Hunter-Ensor, M. & Sinor, J. Brain Res. 544, 196–202 (1991).

    Article  CAS  Google Scholar 

  16. Barbour, B., Brew, H. & Attwell, D. J. Physiol., Lond. 436, 169–193 (1991).

    Article  CAS  Google Scholar 

  17. Barbour, B., Brew, H. & Attwell, D. Nature 335, 433–435 (1988).

    Article  ADS  CAS  Google Scholar 

  18. Romano, P. M., Ahearn, G. A. & Storelli, C. Am. J. Physiol. 257, R180–188 (1989).

    CAS  PubMed  Google Scholar 

  19. Schwartz, E. A. & Tachibana, M. J. Physiol., Lond. 426, 43–80 (1990).

    Article  CAS  Google Scholar 

  20. Tolner, B., Poolman, B., Wallace, B. & Konings, W. N. J. Bact. 174, 2391–2393 (1992).

    Article  CAS  Google Scholar 

  21. Engelke, T., Jording, D., Kapp, D. & Puhler, A. J. Bact. 171, 5551–5560 (1989).

    Article  CAS  Google Scholar 

  22. Deguchi, Y., Yamato, I. & Anraku, Y. J. biol. Chem. 265, 21704–21708 (1990).

    CAS  PubMed  Google Scholar 

  23. Wells, R. G. et al. Am. J. Physiol. 263, F459–465 (1992).

    CAS  PubMed  Google Scholar 

  24. Guastella, J. et al. Science 249, 1303–1306 (1990).

    Article  ADS  CAS  Google Scholar 

  25. Pacholczyk, T., Blakely, R. D. & Amara, S. G. Nature 350, 350–354 (1991).

    Article  ADS  CAS  Google Scholar 

  26. Kilty, J., Lorang, D. & Amara, S. G. Science 254, 78–79 (1991).

    Article  Google Scholar 

  27. Shimada, S. et al. Science 254, 576–578 (1991).

    Article  ADS  CAS  Google Scholar 

  28. Blakely, R. D. et al. Nature 354, 66–70 (1991).

    Article  ADS  CAS  Google Scholar 

  29. Hoffman, B., Mezey, E. & Brownstein, M. J. Science 254, 579–580 (1991).

    Article  ADS  CAS  Google Scholar 

  30. Smith, K. E., Borden, L. A., Hartig, P. R., Branchek, T. & Weinshank, R. L. Neuron 8, 927–935 (1992).

    Article  CAS  Google Scholar 

  31. Fremeau, R. T. Jr, Caron, M. G. & Blakely, R. D. Neuron 8, 915–926 (1992).

    Article  CAS  Google Scholar 

  32. Cotman, C. W., Monaghan, D. T., Ottersen, O. P. & Storm-Mathisen, J. Trends Neurosci. 10, 273–283 (1987).

    Article  CAS  Google Scholar 

  33. Eisen, A. & Calne, D. Can. J. neurol. Sci. 19, 117–123 (1992).

    CAS  PubMed  Google Scholar 

  34. Manev, H., Costa, E., Wroblewski, J. T. & Guidotti, A. FASEB J. 4, 2789–2797 (1990).

    Article  CAS  Google Scholar 

  35. Siesjö, B. K. News Physiol. Sci. 5, 120–125 (1990).

    Google Scholar 

  36. Hagberg, H. et al. J. cereb. Blood Flow Metab. 5, 413–419 (1985).

    Article  CAS  Google Scholar 

  37. Szatkowski, M., Barbour, B. & Attwell, D. Nature 348, 443–446 (1990).

    Article  ADS  CAS  Google Scholar 

  38. Kozak, M. J. Cell Biol. 115, 887–903 (1991).

    Article  CAS  Google Scholar 

  39. Edelman, A. M., Blumenthal, D. K. & Krebs, E. G. A. Rev. Biochem. 56, 567–613 (1987).

    Article  CAS  Google Scholar 

  40. Hediger, M. A., Ikeda, T., Coady, M., Gunderson, C. B. & Wright, E. M. Proc. natn. Acad. Sci. U.S.A. 84, 2634–2637 (1987).

    Article  ADS  CAS  Google Scholar 

  41. Hediger, M. A. Analyt. Biochem. 159, 280–286 (1986).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  43. Kanai, Y. et al. Am. J. Physiol. (in the press).

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kanai, Y., Hediger, M. Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360, 467–471 (1992). https://doi.org/10.1038/360467a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/360467a0

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

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