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.

Regulation of NMDA receptors in cultured hippocampal neurons by protein phosphatases 1 and 2A

Abstract

PHOSPHORYLATION of glutamate receptors is probably an important mechanism for modulating excitatory transmission1–4. However, there is little direct evidence to indicate which protein phosphatases can dephosphorylate glutamate5 or other ligand-gated channels6, although it is known that protein phosphatases 1 and 2A play a major part in modulating voltage7–10 and second-messenger-gated channels11. Here we report that in cultured hippocampal neurons, the N-methyl-D-aspartate (NMDA) receptor can be regulated by endogenous and exogenous serine/threonine protein phosphatases. Phosphatase inhibitors enhanced NMDA currents recorded using the perforated patch technique13 or in cell-attached patches, whereas protein phosphatases 1 or 2A decreased the open probability of these channels in inside-out patches.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. Raymond, L. A., Blackstone, C. D. & Huganir, R. L. Trends Neurosci. 16, 147–153 (1993).

    CAS  Article  Google Scholar 

  2. Ben-Ari, Y., Aniksztejn, L. & Bregestovski, P. Trends Neurosci. 15, 333–339 (1992).

    CAS  Article  Google Scholar 

  3. Swope, S. L., Moss, S. J., Blackstone, C. D. & Huganir, R. L. FASEB J. 6, 2514–2523 (1992).

    CAS  Article  Google Scholar 

  4. Tingley, W. G., Roche, K. W., Thompson, A. K. & Huganir, R. L. Nature 364, 70–73 (1993).

    ADS  CAS  Article  Google Scholar 

  5. Wang, L.-Y., Salter, M. W. & MacDonald, J. F. Science 253, 1132–1135 (1991).

    ADS  CAS  Article  Google Scholar 

  6. Mei, L. & Huganir, R. L. J. biol. Chem. 266, 16063–16072 (1991).

    CAS  PubMed  Google Scholar 

  7. Chung, S., Reinhart, P. H., Martin, B. L., Brautigan, D. & Levitan, I. B. Science 253, 560–562 (1991).

    ADS  CAS  Article  Google Scholar 

  8. White, R. E., Schonbrunn, A. & Armstrong, D. L. Nature 351, 570–573 (1991).

    ADS  CAS  Article  Google Scholar 

  9. Reinhart, P. H., Chung, S., Martin, B. L., Brautigan, D. & Levitan, I. B. J. Neurosci. 11, 1627–1635 (1991).

    CAS  Article  Google Scholar 

  10. White, R. E., Lee, A. B., Shcherbatko, A. D. & Armstrong, D. L. Nature 361, 263–266 (1993).

    ADS  CAS  Article  Google Scholar 

  11. Gordon, S. E., Brautigan, D. L. & Zimmerman, A. L. Neuron 9, 739–748 (1992).

    CAS  Article  Google Scholar 

  12. Horn, R. & Marty, A. J. gen. Physiol. 92, 145–159 (1988).

    CAS  Article  Google Scholar 

  13. Ishihara, H. et al. Biochem. biophys. Res. Commun. 159, 871–877 (1989).

    CAS  Article  Google Scholar 

  14. Kateo, Y., Fusetani, N., Matsunaga, S. & Hashimoto, S. J. Am. chem. Soc. 108, 2780–2781 (1986).

    Article  Google Scholar 

  15. Suganuma, M. et al. Cancer Res. 50, 3521–3525 (1990).

    CAS  PubMed  Google Scholar 

  16. Cohen, P., Holmes, C. F. B. & Tsukitani, Y. Trends biochem. Sci. 15, 98–102 (1990).

    CAS  Article  Google Scholar 

  17. Johnson, J. W. & Ascher, P. J. Physiol., Lond. 455, 339–365 (1992).

    CAS  Article  Google Scholar 

  18. Benveniste, M., Clements, J., Vyklicky, L. & Mayer, M. L. J. Physiol., Lond. 428, 333–357 (1990).

    CAS  Article  Google Scholar 

  19. Nairn, A. C. & Shenolikar, S. Curr. Opin. Neurobiol. 2, 296–301 (1992).

    CAS  Article  Google Scholar 

  20. Cohen, P. Rev. Biochem. 58, 453–508 (1989).

    CAS  Article  Google Scholar 

  21. Rosenmund, C. & Westbrook, G. L. Neuron 10, 805–814 (1993).

    CAS  Article  Google Scholar 

  22. Eriksson, J. E. et al. Proc. natn. Acad. Sci. U.S.A. 89, 11093–11097 (1992).

    ADS  CAS  Article  Google Scholar 

  23. Huang, F. L. & Glinsmann, W. H. Eur. J. Biochem. 70, 419–426 (1976).

    CAS  Article  Google Scholar 

  24. Clements, J. D. et al. Science 258, 1498–1501 (1992).

    ADS  CAS  Article  Google Scholar 

  25. Johnson, J. W. & Ascher, P. Nature 325, 529–531 (1987).

    ADS  CAS  Article  Google Scholar 

  26. Oh, Y. & Benos, D. J. Am. J. Physiol. 264, C1489–C1499 (1993).

    CAS  Article  Google Scholar 

  27. Orser, B. A. & MacDonald, J. F. Can. J. Anaesth. 40, A61 (1993).

    Google Scholar 

  28. Chen, J., Martin, B. L. & Brautigan, D. L. Science 257, 1261–1264 (1992).

    ADS  CAS  Article  Google Scholar 

  29. Brautigan, D. L., Shriner, C. L. & Gruppuso, P. A. J. biol. Chem. 260, 4295–4302 (1985).

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wang, LY., Orser, B., Brautigan, D. et al. Regulation of NMDA receptors in cultured hippocampal neurons by protein phosphatases 1 and 2A. Nature 369, 230–232 (1994). https://doi.org/10.1038/369230a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/369230a0

Further reading

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