Changing subunit composition of heteromeric NMDA receptors during development of rat cortex (original) (raw)

Nature volume 368, pages 144–147 (1994)Cite this article

Abstract

ACTIVATION of the _N_-methyl-d-aspartate (NMDA) receptor is important for certain forms of activity-dependent synaptic plasticity, such as long-term potentiation (reviewed in ref. 1), and the patterning of connections during development of the visual system (reviewed in refs 2, 3). Several subunits of the NMDA receptor have been cloned: these are NMDAR1 (NR1), and NMDAR2A, 2B, 2C and 2D (NR2A-D)4–8. Based on heterologous co-expression studies, it is inferred that NR1 encodes an essential subunit of NMDA receptors and that functional diversity of NMDA receptors in vivo is effected by differential incorporation of subunits NR2A–NR2D5–8. Little is known, however, about the actual subunit composition or heterogeneity of NMDA receptors in the brain. By co-immunoprecipitation with subunit-specific antibodies, we present here direct evidence that NMDA receptors exist in rat neocortex as heteromeric complexes of considerable heterogeneity, some containing both NR2A and NR2B subunits. A progressive alteration in subunit composition seen postnatally could contribute to NMDA-receptor variation and changing synaptic plasticity during cortical development.

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References

  1. Bliss, r. V. P. & Collingridge, G. L. Nature 361, 31–39 (1993).
    Article ADS CAS Google Scholar
  2. Constantine-Paton, M., Cline, H. T. & Debski, E. A. Rev. Neurosci. 13, 129–154 (1990).
    Article CAS Google Scholar
  3. Schatz, C. J. Neuron 5, 745–756 (1990).
    Article Google Scholar
  4. Moriyoshi, K. et al. Nature 354, 31–37 (1991).
    Article ADS CAS Google Scholar
  5. Monyer, H. et al. Science 256, 1217–1221 (1992).
    Article ADS CAS Google Scholar
  6. Meguro, H. et al. Nature 357, 70–74 (1992).
    Article ADS CAS Google Scholar
  7. Kutsuwada, T. et al. Nature 358, 36–41 (1992).
    Article ADS CAS Google Scholar
  8. Ishii, T. et al. J. biol. Chem. 268, 2836–2843 (1993).
    CAS Google Scholar
  9. Hollmann, M. et al. Neuron 10, 943–954 (1993).
    Article CAS Google Scholar
  10. Sugihara, H. et al. Biochem. biophys. Res. Commun. 185, 826–832 (1992).
    Article CAS Google Scholar
  11. Tingley, W. G., Roche, K. W., Thompson, A. K. & Huganir, R. L. Nature 364, 70–73 (1993).
    Article ADS CAS Google Scholar
  12. Chazot, P. L., Cik, M. & Stephenson, F. A. J. Neurochem. 59, 1176–1178 (1992).
    Article CAS Google Scholar
  13. Stern, P., Behe, P., Schoepfer, R. & Colquhoun, D. Proc. R. Soc. Lond. B250, 271–277 (1992).
    Article ADS CAS Google Scholar
  14. Carmignoto, G. & Vicini, S. Science 258, 1007–1011 (1992).
    Article ADS CAS Google Scholar
  15. Hestrin, S. Nature 357, 686–689 (1992).
    Article ADS CAS Google Scholar
  16. Ben-Ari, Y. et al. Neurosci. Lett. 94, 88–92 (1988).
    Article CAS Google Scholar
  17. Kato, N., Artoloa, A. & Singer, W. Devl. Brain Res. 60, 43–50 (1991).
    Article CAS Google Scholar
  18. Kleckner, N. W. & Dingledine, R. Molec. Brain Res. 11, 151–159 (1991).
    CAS PubMed Google Scholar
  19. Tsumoto, T., Hagihara, K., Sato, H. & Hata, Y. Nature 327, 513–514 (1987).
    Article ADS CAS Google Scholar
  20. Watanabe, M. et al. Neuroreport 3, 1138–1140 (1992).
    Article CAS Google Scholar
  21. Williams, K., Russell, S. L., Shen, Y. M. & Molinoff, P. B. Neuron 10, 267–278 (1993).
    Article CAS Google Scholar
  22. Kato, N. & Yoshimura, H. Proc. natn. Acad. Sci. U.S.A. 90, 7114–7118 (1993).
    Article ADS CAS Google Scholar
  23. Nakanishi, N., Axel, R. & Schneider, R. Proc. natn. Acad. Sci. U.S.A. 89, 8552–8556 (1992).
    Article ADS CAS Google Scholar
  24. Durand, G. M. et al. Proc. natn. Acad. Sci. U.S.A. 89, 9359–9363 (1992).
    Article ADS CAS Google Scholar
  25. Anantharam, V. et al. FEBS Lett. 305, 27–30 (1992).
    Article CAS Google Scholar
  26. Sheng, M., Tsaur, M-L., Jan, Y. N. & Jan, L. Y. Neuron 9, 271–284 (1992).
    Article CAS Google Scholar
  27. Sheng, M., Liao, Y. J., Jan, Y. N. & Jan, L. Y. Nature 365, 72–75 (1993).
    Article ADS CAS Google Scholar
  28. Tsaur, M-L., et al. Neuron 8, 1055–1067 (1992).
    Article CAS Google Scholar

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Authors and Affiliations

  1. Howard Hughes Medical Institute and Departments of Physiology and Biochemistry, University of California, San Francisco, California, 94143-0724, USA
    Morgan Sheng, Jennifer Cummings, Leslie Ann Roldan, Yuh Nung Jan & Lily Yeh Jan

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  1. Morgan Sheng
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  2. Jennifer Cummings
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  3. Leslie Ann Roldan
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  4. Yuh Nung Jan
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  5. Lily Yeh Jan
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Sheng, M., Cummings, J., Roldan, L. et al. Changing subunit composition of heteromeric NMDA receptors during development of rat cortex.Nature 368, 144–147 (1994). https://doi.org/10.1038/368144a0

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