Competitive binding of α-actinin and calmodulin to the NMDA receptor

Abstract

The mechanisms by which neurotransmitter receptors are immobilized at postsynaptic sites in neurons are largely unknown. The activity of NMDA (N-methyl-D-aspartate) receptors is mechanosensitive1 and dependent on the integrity of actin2, suggesting a functionally important interaction between NMDA receptors and the postsynaptic cytoskeleton. α-Actinin-2, a member of the spectrin/dystrophin family of actin-binding proteins, is identified here as a brain postsynaptic density protein that colocalizes in dendritic spines with NMDA receptors and the putative NMDA receptor-clustering molecule PSD-95. α-Actinin-2 binds by its central rod domain to the cytoplasmic tail of both NR1 and NR2B subunits of the NMDA receptor, and can be immunoprecipitated with NMDA receptors and PSD-95 from rat brain. Intriguingly, NR1-α-actinin binding is directly antagonized by Ca2+/calmodulin. Thus α-actinin may play a role in both the localization of NMDA receptors and their modulation by Ca2+.

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References

  1. 1

    Paoletti, P. & Ascher, P. Neuron 13, 645–655 (1994).

  2. 2

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

  3. 3

    Ishii, T. et al. J. Biol. Chem. 268, 2836–2843 (1992).

  4. 4

    Meguro, H. et al. Nature 357, 70–73 (1992).

  5. 5

    Monyer, H. et al. Science 256, 1217–1221 (1992).

  6. 6

    Kutsuwada, T. et al. Nature 358, 36–41 (1993).

  7. 7

    Monyer, H., Burnashev, N., Laurie, D. J., Sakmann, B. & Seeburg, P. H. Neuron 12, 529–540 (1994).

  8. 8

    Sheng, M., Cummings, J., Roldan, L. A., Jan, Y. N. & Jan, L. Y. Nature 368, 144–147 (1994).

  9. 9

    Kornau, H.-C., Schenker, L. T., Kennedy, M. B. & Seeburg, P. H. Science 269, 1737–1740 (1995).

  10. 10

    Niethammer, M., Kim, E. & Sheng, M. J. Neurosci. 16, 2157–2163 (1996).

  11. 11

    Ehlers, M. D., Tingley, W. G. & Huganir, R. L. Science 269, 1734–1737 (1995).

  12. 12

    Sugihara, H., Moriyoshi, K., Ishii, T., Masu, M. & Nakanishi, S. Biochem. Biophys. Res. Commun. 185, 826–832 (1992).

  13. 13

    Beggs, A. H. et al. J. Biol. Chem. 267, 9281–9288 (1992).

  14. 14

    Bennett, V. Physiol. Rev. 70, 1029–1065 (1990).

  15. 15

    Blanchard, A., Ohanian, V. & Critchley, D. J. Muscle Res. Cell Motil. 10, 280–289 (1989).

  16. 16

    Hollmann, M. et al. Neuron 10, 943–954 (1993).

  17. 17

    Kim, E., Cho, K.-O., Rothschild, A. & Sheng, M. Neuron 17, 103–113 (1996).

  18. 18

    Müller, B. M. et al. J. Neurosci. 15, 2354–2366 (1995).

  19. 19

    Miller, S. G. & Kennedy, M. B. J. Biol. Chem. 260, 9039–9046 (1985).

  20. 20

    Ehlers, M. D., Zhang, S., Bernhardt, J. P. & Huganir, R. L. Cell 84, 745–755 (1996).

  21. 21

    Kim, E., Niethammer, M., Rothschild, A., Jan, Y. N. & Sheng, M. Nature 378, 85–88 (1995).

  22. 22

    Li, M., Jan, Y. N. & Jan, L. Y. Science 257, 1225–1230 (1992).

  23. 23

    Müller, B. M. et al. Neuron 17, 255–265 (1996).

  24. 24

    Banker, G. A. & Cowan, W. M. Brain Res. 126, 397–425 (1977).

  25. 25

    Moriyoshi, K. et al. Nature 354, 31–37 (1991).

  26. 26

    Cho, K.-O., Hunt, C. A. & Kennedy, M. B. Neuron 9, 929–942 (1992).

  27. 27

    Moon, I. S., Apperson, M. L. & Kennedy, M. B. Proc. Natl Acad. Sci. USA 91, 3954–3958 (1994).

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