RGD Reference Report - Rabphilin 3A retains NMDA receptors at synaptic sites through interaction with GluN2A/PSD-95 complex. - Rat Genome Database

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Rabphilin 3A retains NMDA receptors at synaptic sites through interaction with GluN2A/PSD-95 complex.

Authors: Stanic, J  Carta, M  Eberini, I  Pelucchi, S  Marcello, E  Genazzani, AA  Racca, C  Mulle, C  Di Luca, M  Gardoni, F 
Citation: Stanic J, etal., Nat Commun. 2015 Dec 18;6:10181. doi: 10.1038/ncomms10181.
RGD ID: 11085451
Pubmed: PMID:26679993   (View Abstract at PubMed)
PMCID: PMC4703873   (View Article at PubMed Central)
DOI: DOI:10.1038/ncomms10181   (Journal Full-text)

NMDA receptor (NMDAR) composition and synaptic retention represent pivotal features in the physiology and pathology of excitatory synapses. Here, we identify Rabphilin 3A (Rph3A) as a new GluN2A subunit-binding partner. Rph3A is known as a synaptic vesicle-associated protein involved in the regulation of exo- and endocytosis processes at presynaptic sites. We find that Rph3A is enriched at dendritic spines. Protein-protein interaction assays reveals that Rph3A N-terminal domain interacts with GluN2A(1349-1389) as well as with PSD-95(PDZ3) domains, creating a ternary complex. Rph3A silencing in neurons reduces the surface localization of synaptic GluN2A and NMDAR currents. Moreover, perturbing GluN2A/Rph3A interaction with interfering peptides in organotypic slices or in vivo induces a decrease of the amplitude of NMDAR-mediated currents and GluN2A density at dendritic spines. In conclusion, Rph3A interacts with GluN2A and PSD-95 forming a complex that regulates NMDARs stabilization at postsynaptic membranes.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dendritic spine organization involved_inIMP 11085451; 11085451; 11085451PMID:26679993UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dendritic spine located_inIDA 11085451; 11085451; 11085451PMID:26679993UniProt 
postsynaptic membrane located_inIDA 11085451; 11085451; 11085451PMID:26679993UniProt 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Dlg4  (discs large MAGUK scaffold protein 4)
Grin2a  (glutamate ionotropic receptor NMDA type subunit 2A)
Rph3a  (rabphilin 3A)


Additional Information