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Updated: Jun 2, 2026
04:48
A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
Molecular determinants controlling NMDA receptor synaptic incorporation
Granville P Storey1, Ximena Opitz-Araya, Andres Barria
1Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington 98195-7290, USA.
Summary
A novel N-glycosylation site on GluN2B subunits drives the synaptic incorporation of NMDA receptors (NMDARs) independently of neuronal activity, revealing a new trafficking mechanism.
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- Synaptic plasticity relies on the precise regulation of NMDA receptor (NMDAR) trafficking.
- Different NMDAR subunits, GluN2A and GluN2B, exhibit distinct synaptic incorporation mechanisms: GluN2B is constitutive, while GluN2A is activity-dependent.
Purpose of the Study:
- To elucidate the molecular determinants governing the differential synaptic incorporation of NMDARs.
- To identify the specific features of GluN2 subunits that dictate their trafficking pathways.
Main Methods:
- Utilized electrophysiologically tagged NMDARs in rat hippocampal slices.
- Employed chimeric GluN2 subunit constructs to map functional domains.
- Investigated the role of post-translational modifications in receptor trafficking.
Main Results:
- Identified a putative N-glycosylation site unique to the GluN2B subunit.
- Demonstrated that this N-glycosylation site is both necessary and sufficient for activity-independent synaptic NMDAR incorporation.
- Showcased that GluN2A-containing NMDARs lack this site and exhibit activity-dependent incorporation.
Conclusions:
- A novel mechanism involving N-glycosylation regulates NMDAR synaptic trafficking.
- This finding provides new insights into the molecular basis of synaptic plasticity and NMDAR function.
- The identified site offers a potential target for modulating NMDAR-dependent synaptic changes.
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