Allosteric Interactions between NMDA Receptor Subunits Shape the Developmental Shift in Channel Properties

Weinan Sun; Kasper B. Hansen; Craig E. Jahr

doi:10.1016/j.neuron.2017.03.018

Allosteric Interactions between NMDA Receptor Subunits Shape the Developmental Shift in Channel Properties

Weinan Sun, Kasper B. Hansen, Craig E. Jahr

Vollum Institute

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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.

Original language	English (US)
Pages (from-to)	58-64.e3
Journal	Neuron
Volume	94
Issue number	1
DOIs	https://doi.org/10.1016/j.neuron.2017.03.018
State	Published - Apr 5 2017

Keywords

GluN2 subunit
Triheteromeric NMDA receptors
allosteric interaction
amino-terminal domain
crosslinking
excitatory synaptic transmission
glutamate
open probability
receptor deactivation

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2017.03.018

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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.",

keywords = "GluN2 subunit, Triheteromeric NMDA receptors, allosteric interaction, amino-terminal domain, crosslinking, excitatory synaptic transmission, glutamate, open probability, receptor deactivation",

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Allosteric Interactions between NMDA Receptor Subunits Shape the Developmental Shift in Channel Properties

Abstract

Keywords

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