title: Allosteric Interactions between NMDA Receptor Subunits Shape the Developmental Shift in Channel Properties.
abstract: During development of the central nervous system, there is a shift in the subunit composition of NMDA receptors (NMDARs) resulting in a dramatic acceleration of NMDAR-mediated synaptic currents. This shift coincides with upregulation of the GluN2A subunit and triheteromeric GluN1/2A/2B receptors with fast deactivation kinetics, whereas expression of diheteromeric GluN1/2B receptors with slower deactivation kinetics is decreased. Here, we show that allosteric interactions occur between the glutamate-binding GluN2 subunits in triheteromeric GluN1/2A/2B NMDARs. This allosterism is dominated by the GluN2A subunit and results in functional properties not predicted by those of diheteromeric GluN1/2A and GluN1/2B NMDARs. These findings suggest that GluN1/2A/2B NMDARs may maintain some signaling properties of the GluN2B subunit while having the kinetic properties of GluN1/2A NMDARs and highlight the complexity in NMDAR signaling created by diversity in subunit composition.
authors.affiliation: Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA.
authors.forename: Weinan
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Montana, 32 Campus Dr., Missoula, MT 59812, USA.
authors.forename: Kasper B
authors.initials: KB
authors.lastname: Hansen
authors.affiliation: Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA. Electronic address: jahr@ohsu.edu.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Jahr
mesh_terms: D000494:Allosteric Regulation / Q000235:genetics*; D000818:Animals; D004721:Endoplasmic Reticulum; D018507:Gene Expression Regulation, Developmental; D018698:Glutamic Acid / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009473:Neuronal Plasticity; D009865:Oocytes / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D021122:Protein Subunits; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission; D014982:Xenopus laevis
chemical_list: D018698:Glutamic Acid; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor
keywords: GluN2 subunit; Triheteromeric NMDA receptors; allosteric interaction; amino-terminal domain; crosslinking; excitatory synaptic transmission; glutamate; open probability; receptor deactivation