NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation

102Citations
Citations of this article
214Readers
Mendeley users who have this article in their library.

This article is free to access.

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.

Cite

CITATION STYLE

APA

Frank, R. A. W., Komiyama, N. H., Ryan, T. J., Zhu, F., O’Dell, T. J., & Grant, S. G. N. (2016). NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation. Nature Communications, 7. https://doi.org/10.1038/ncomms11264

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free