RGD Reference Report - Surface dynamics of GluN2B-NMDA receptors controls plasticity of maturing glutamate synapses. - Rat Genome Database

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Surface dynamics of GluN2B-NMDA receptors controls plasticity of maturing glutamate synapses.

Authors: Dupuis, JP  Ladepeche, L  Seth, H  Bard, L  Varela, J  Mikasova, L  Bouchet, D  Rogemond, V  Honnorat, J  Hanse, E  Groc, L 
Citation: Dupuis JP, etal., EMBO J. 2014 Apr 16;33(8):842-61. doi: 10.1002/embj.201386356. Epub 2014 Mar 3.
RGD ID: 10047343
Pubmed: PMID:24591565   (View Abstract at PubMed)
PMCID: PMC4194110   (View Article at PubMed Central)
DOI: DOI:10.1002/embj.201386356   (Journal Full-text)

NMDA-type glutamate receptors (NMDAR) are central actors in the plasticity of excitatory synapses. During adaptive processes, the number and composition of synaptic NMDAR can be rapidly modified, as in neonatal hippocampal synapses where a switch from predominant GluN2B- to GluN2A-containing receptors is observed after the induction of long-term potentiation (LTP). However, the cellular pathways by which surface NMDAR subtypes are dynamically regulated during activity-dependent synaptic adaptations remain poorly understood. Using a combination of high-resolution single nanoparticle imaging and electrophysiology, we show here that GluN2B-NMDAR are dynamically redistributed away from glutamate synapses through increased lateral diffusion during LTP in immature neurons. Strikingly, preventing this activity-dependent GluN2B-NMDAR surface redistribution through cross-linking, either with commercial or with autoimmune anti-NMDA antibodies from patient with neuropsychiatric symptoms, affects the dynamics and spine accumulation of CaMKII and impairs LTP. Interestingly, the same impairments are observed when expressing a mutant of GluN2B-NMDAR unable to bind CaMKII. We thus uncover a non-canonical mechanism by which GluN2B-NMDAR surface dynamics plays a critical role in the plasticity of maturing synapses through a direct interplay with CaMKII.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:Q0096010047343PMID:24591565IntAct 
protein binding enablesIPIUniProtKB:P1127510047343PMID:24591565IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Camk2a  (calcium/calmodulin-dependent protein kinase II alpha)
Grin2b  (glutamate ionotropic receptor NMDA type subunit 2B)


Additional Information