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Link to original content: https://doi.org/10.1038/76615
Proteomic analysis of NMDA receptor–adhesion protein signaling complexes | Nature Neuroscience
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Proteomic analysis of NMDA receptor–adhesion protein signaling complexes

Nature Neuroscience volume 3, pages 661–669 (2000)Cite this article

Abstract

N-methyl-D-aspartate receptors (NMDAR) mediate long-lasting changes in synapse strength via downstream signaling pathways. We report proteomic characterization with mass spectrometry and immunoblotting of NMDAR multiprotein complexes (NRC) isolated from mouse brain. The NRC comprised 77 proteins organized into receptor, adaptor, signaling, cytoskeletal and novel proteins, of which 30 are implicated from binding studies and another 19 participate in NMDAR signaling. NMDAR and metabotropic glutamate receptor subtypes were linked to cadherins and L1 cell-adhesion molecules in complexes lacking AMPA receptors. These neurotransmitter–adhesion receptor complexes were bound to kinases, phosphatases, GTPase-activating proteins and Ras with effectors including MAPK pathway components. Several proteins were encoded by activity-dependent genes. Genetic or pharmacological interference with 15 NRC proteins impairs learning and with 22 proteins alters synaptic plasticity in rodents. Mutations in three human genes (NF1, Rsk-2, L1) are associated with learning impairments, indicating the NRC also participates in human cognition.

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Figure 1: Basic composition of NRC isolated from mouse brain.
Figure 2: Mass spectrometry analysis of the NRC.

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Acknowledgements

Antibodies were provided by those listed in Methods. We thank T.J. O'Dell and P. Brophy for comments. H.H. and S.G. were supported by the Wellcome Trust.

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Authors and Affiliations

  1. Centre for Genome Research, Centre for Neuroscience, University of Edinburgh, West Mains Road, Edinburgh , EH9 3JQ, UK

    Holger Husi & Seth G. N. Grant

  2. Glaxo Wellcome Research and Development Ltd, Gunnels Wood Road, Stevenage, SG1 2NY, UK

    Malcolm A. Ward, Jyoti S. Choudhary & Walter P. Blackstock

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  1. Holger Husi
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Correspondence to Seth G. N. Grant.

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Husi, H., Ward, M., Choudhary, J. et al. Proteomic analysis of NMDA receptor–adhesion protein signaling complexes. Nat Neurosci 3, 661–669 (2000). https://doi.org/10.1038/76615

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