The Developmental Shift of NMDA Receptor Composition Proceeds Independently of GluN2 Subunit-Specific GluN2 C-Terminal Sequences.
The GluN2 subtype (2A versus 2B) determines biophysical properties and signaling of forebrain NMDA receptors (NMDARs). During development, GluN2A becomes incorporated into previously GluN2B-dominated NMDARs. This "switch" is proposed to be driven by distinct features of GluN2 cytoplasmic C-terminal domains (CTDs), including a unique CaMKII interaction site in GluN2B that drives removal from the synapse. However, these models remain untested in the context of endogenous NMDARs. We show that, although mutating the endogenous GluN2B CaMKII site has secondary effects on GluN2B CTD phosphorylation, the developmental changes in NMDAR composition occur normally and measures of plasticity and synaptogenesis are unaffected. Moreover, the switch proceeds normally in mice that have the GluN2A CTD replaced by that of GluN2B and commences without an observable decline in GluN2B levels but is impaired by GluN2A haploinsufficiency. Thus, GluN2A expression levels, and not GluN2 subtype-specific CTD-driven events, are the overriding factor in the developmental switch in NMDAR composition.
['McKay|Sean|S|', 'Ryan|Tomás J|TJ|', 'McQueen|Jamie|J|', 'Indersmitten|Tim|T|', 'Marwick|Katie F M|KFM|', 'Hasel|Philip|P|', 'Kopanitsa|Maksym V|MV|', 'Baxter|Paul S|PS|', 'Martel|Marc-André|MA|', 'Kind|Peter C|PC|', 'Wyllie|David J A|DJA|', "O'Dell|Thomas J|TJ|", 'Grant|Seth G N|SGN|', 'Hardingham|Giles E|GE|', 'Komiyama|Noboru H|NH|']
D000595:Amino Acid Sequence D000818:Animals D001665:Binding Sites D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 D017774:Long-Term Potentiation D008810:Mice, Inbred C57BL D009154:Mutation D055495:Neurogenesis D010766:Phosphorylation D021122:Protein Subunits D051381:Rats D016194:Receptors, N-Methyl-D-Aspartate D013569:Synapses D013826:Theta Rhythm
NMDA receptor synaptogenesis neurodevelopment synaptic plasticity