Molecular determinants controlling NMDA receptor synaptic incorporation

• Published in: The Journal of neuroscience 2011-04, Vol.31 (17), p.6311-6316
• Main Authors: Storey, Granville P, Opitz-Araya, Ximena, Barria, Andres
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Biophysics; Brief Communications; Electric Stimulation - methods; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - genetics; Excitatory Postsynaptic Potentials - physiology; Green Fluorescent Proteins - genetics; Hippocampus - cytology; Macromolecular Substances - chemistry; Male; Mutation - genetics; Neurons - physiology; Organ Culture Techniques; Patch-Clamp Techniques - methods; Protein Subunits; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - chemistry; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - physiology; Synapses - physiology; Time Factors; Transfection - methods; Valine - analogs & derivatives; Valine - pharmacology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.5553-10.2011

Synaptic incorporation of NMDA receptors (NMDARs) is regulated by GluN2 subunits with different rules controlling GluN2A- and GluN2B-containing receptors; whereas GluN2B-containing receptors are constitutively incorporated into synapses, GluN2A incorporation is activity-dependent. We expressed electrophysiologically tagged NMDARs in rat hippocampal slices to identify the molecular determinants controlling the mode of synaptic incorporation of NMDARs. Expressing chimeric GluN2 subunits, we identified a putative N-glycosylation site present in GluN2B, but not in GluN2A, as necessary and sufficient to drive NMDARs into synapses in an activity-independent manner. This suggests a novel mechanism for regulating activity-driven changes and trafficking of NMDARs to the synapse.