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 |
|---|---|
| Pages (from-to) | 58-64.e3 |
| Journal | Neuron |
| Volume | 94 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 5 2017 |
Funding
We thank Brett Carter and Delia Chiu from the Jahr laboratory and Gina Bullard, Feng Yi, and Genevieve Lind from the Hansen laboratory for their helpful discussions and technical assistance. This work was supported by the National Institutes of Health (R21NS091337, P20GM103546, and R01NS097536).
| Funder number |
|---|
| R01NS097536, P20GM103546 |
| R21NS091337 |
Keywords
- GluN2 subunit
- Triheteromeric NMDA receptors
- allosteric interaction
- amino-terminal domain
- crosslinking
- excitatory synaptic transmission
- glutamate
- open probability
- receptor deactivation