NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation
Citations Over TimeTop 10% of 2016 papers
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.
Related Papers
- → Nitric oxide-induced blockade of NMDA receptors(1992)450 cited
- → Hippocampal neuronal responsiveness to NMDA agonists and antagonists in the adult rat neonatally treated with MK-801(1992)34 cited
- → The Effects of Epidural κ Agonist and NMDA Antagonist: Discussions and Hypotheses(2008)
- → Behavioral Characteristics of GRIN3A-overexpressing Transgenic Mice(2016)
- → Μελέτη των κρίσιμων περιόδων μεταγεννητικής ανάπτυξης που εξαρτώνται από τους NMDA υποδοχείς και επηρεάζουν τη λειτουργία του προμετωπιαίου φλοιού και του ιππόκαμπου(2023)