Frank, RAW orcid.org/0000-0001-9724-9547, Komiyama, NH, Ryan, TJ et al. (3 more authors) (2016) NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation. Nature Communications, 7. 11264. p. 11264.
Abstract
How neuronal proteomes self-organize is poorly understood because of their inherent molecular and cellular complexity. Here, focusing on mammalian synapses we use blue-native PAGE and ‘gene-tagging’ of GluN1 to report the first biochemical purification of endogenous
NMDA receptors (NMDARs) directly from adult mouse brain. We show that NMDARs partition between two discrete populations of receptor complexes and B1.5MDa supercomplexes.
We tested the assembly mechanism with six mouse mutants, which
indicates a tripartite requirement of GluN2B, PSD93 and PSD95 gate the incorporation of receptors into B1.5MDa supercomplexes, independent of either canonical PDZ-ligands or GluN2A. Supporting the essential role of GluN2B, quantitative gene-tagging revealed a fourfold molar excess of GluN2B over GluN2A in adult forebrain. NMDAR supercomplexes
are assembled late in postnatal development and triggered by synapse maturation involving epigenetic and activity-dependent mechanisms. Finally, screening the quaternary organization of 60 native proteins identified numerous discrete supercomplexes that populate the
mammalian synapse.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018, Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 19 Sep 2018 11:42 |
Last Modified: | 16 Sep 2020 15:30 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/ncomms11264 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:135852 |