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

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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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Author notes

  1. Anuradha Rao and Ann Marie Craig: Department of Cell and Structural Biology, University of Illinois, Urbana-Champaign, Illinois 61801, USA

  2. Alan H. Beggs: Genetics Division, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA

Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Neurobiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, 02114, USA

    Michael Wyszynski, Jerry Lin, Anuradha Rao, Elizabeth Nigh, Alan H. Beggs, Ann Marie Craig & Morgan Sheng

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  1. Michael Wyszynski
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  2. Jerry Lin
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  3. Anuradha Rao
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  4. Elizabeth Nigh
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  5. Alan H. Beggs
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  6. Ann Marie Craig
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  7. Morgan Sheng
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Wyszynski, M., Lin, J., Rao, A. et al. Competitive binding of α-actinin and calmodulin to the NMDA receptor. Nature 385, 439–442 (1997). https://doi.org/10.1038/385439a0

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