NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation
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Frank-2016-NMDA receptors.pdf
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Author(s)
Frank, René A. W.
Komiyama, Noboru H.
Ryan, Tomas John
Zhu, Fei
O’Dell, Thomas J.
Grant, Seth G. N.
Date Issued
April 2016
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Frank, Rene A. W., Noboru H. Komiyama, Tomás J. Ryan, Fei Zhu, Thomas J. O’Dell and Seth G. N. Grant. "NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation." Nature Communications 7, article number 11264 (April 2016), p.1-13.
Version
Final published version
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 ~1.5 MDa 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 ~1.5 MDa 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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DOI of Published Version
https://doi.org/10.1038/ncomms11264
