RGD Reference Report - Activity-induced synaptic delivery of the GluN2A-containing NMDA receptor is dependent on endoplasmic reticulum chaperone Bip and involved in fear memory. - Rat Genome Database

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Activity-induced synaptic delivery of the GluN2A-containing NMDA receptor is dependent on endoplasmic reticulum chaperone Bip and involved in fear memory.

Authors: Zhang, XM  Yan, XY  Zhang, B  Yang, Q  Ye, M  Cao, W  Qiang, WB  Zhu, LJ  Du, YL  Xu, XX  Wang, JS  Xu, F  Lu, W  Qiu, S  Yang, W  Luo, JH 
Citation: Zhang XM, etal., Cell Res. 2015 Jul;25(7):818-36. doi: 10.1038/cr.2015.75. Epub 2015 Jun 19.
RGD ID: 11096590
Pubmed: PMID:26088419   (View Abstract at PubMed)
PMCID: PMC4493282   (View Article at PubMed Central)
DOI: DOI:10.1038/cr.2015.75   (Journal Full-text)

The N-methyl-D-aspartate receptor (NMDAR) in adult forebrain is a heterotetramer mainly composed of two GluN1 subunits and two GluN2A and/or GluN2B subunits. The synaptic expression and relative numbers of GluN2A- and GluN2B-containing NMDARs play critical roles in controlling Ca(2+)-dependent signaling and synaptic plasticity. Previous studies have suggested that the synaptic trafficking of NMDAR subtypes is differentially regulated, but the precise molecular mechanism is not yet clear. In this study, we demonstrated that Bip, an endoplasmic reticulum (ER) chaperone, selectively interacted with GluN2A and mediated the neuronal activity-induced assembly and synaptic incorporation of the GluN2A-containing NMDAR from dendritic ER. Furthermore, the GluN2A-specific synaptic trafficking was effectively disrupted by peptides interrupting the interaction between Bip and GluN2A. Interestingly, fear conditioning in mice was disrupted by intraperitoneal injection of the interfering peptide before training. In summary, we have uncovered a novel mechanism for the activity-dependent supply of synaptic GluN2A-containing NMDARs, and demonstrated its relevance to memory formation.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
long-term synaptic potentiation  IEP 11096590; 11096590; 11096590 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell surface  IDA 11096590; 11096590; 11096590MMO:0000686 RGD 
dendritic shaft  IDA 11096590MMO:0000686RGD 
neuronal cell body  IDA 11096590MMO:0000686RGD 
postsynaptic density, intracellular component  IDA 11096590; 11096590; 11096590MMO:0000679RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gria1  (glutamate ionotropic receptor AMPA type subunit 1)
Grin2a  (glutamate ionotropic receptor NMDA type subunit 2A)
Grin2b  (glutamate ionotropic receptor NMDA type subunit 2B)
Hspa5  (heat shock protein family A (Hsp70) member 5)


Additional Information