title: Molecular determinants controlling NMDA receptor synaptic incorporation.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington 98195-7290, USA.
authors.forename: Granville P
authors.initials: GP
authors.lastname: Storey
authors.forename: Ximena
authors.initials: X
authors.lastname: Opitz-Araya
authors.forename: Andres
authors.initials: A
authors.lastname: Barria
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D046911:Macromolecular Substances / Q000737:chemistry; D008297:Male; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques / Q000379:methods; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D046911:Macromolecular Substances; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D049452:Green Fluorescent Proteins; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine