RGD Reference Report - Fyn-mediated phosphorylation of NR2B Tyr-1336 controls calpain-mediated NR2B cleavage in neurons and heterologous systems. - Rat Genome Database

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Fyn-mediated phosphorylation of NR2B Tyr-1336 controls calpain-mediated NR2B cleavage in neurons and heterologous systems.

Authors: Wu, Hai-Yan  Hsu, Fu-Chun  Gleichman, Amy J  Baconguis, Isabelle  Coulter, Douglas A  Lynch, David R 
Citation: Wu HY, etal., J Biol Chem. 2007 Jul 13;282(28):20075-87. doi: 10.1074/jbc.M700624200. Epub 2007 May 25.
RGD ID: 13506268
Pubmed: PMID:17526495   (View Abstract at PubMed)
PMCID: PMC2464284   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M700624200   (Journal Full-text)

Cleavage of the intracellular carboxyl terminus of the N-methyl-d-aspartate (NMDA) receptor 2 subunit (NR2) by calpain regulates NMDA receptor function and localization. Here, we show that Fyn-mediated phosphorylation of NR2B controls calpain-mediated NR2B cleavage. In cultured neurons, calpain-mediated NR2B cleavage is significantly attenuated by blocking NR2B phosphorylation of Tyr-1336, but not Tyr-1472, via inhibition of Src family kinase activity or decreasing Fyn levels by small interfering RNA. In HEK cells, mutation of Tyr-1336 eliminates the potentiating effect of Fyn on calpain-mediated NR2B cleavage. The potentiation of NR2B cleavage by Fyn is limited to cell surface receptors and is associated with calpain translocation to plasma membranes during NMDA receptor activation. Finally, reducing full-length NR2B by calpain does not decrease extrasynaptic NMDA receptor function, and truncated NR1/2B receptors similar to those generated by calpain have electrophysiological properties matching those of wild-type receptors. Thus, the Fyn-controlled regulation of NMDA receptor cleavage by calpain may play critical roles in controlling NMDA receptor properties during synaptic plasticity and excitotoxicity.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to glycine involved_inIMP 13506268PMID:17526495ARUK-UCL 
cellular response to L-glutamate involved_inIMP 13506268PMID:17526495ARUK-UCL 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell surface located_inIDA 13506268; 13506268PMID:17526495ARUK-UCL 
cytoplasm located_inIDA 13506268; 13506268PMID:17526495ARUK-UCL 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein tyrosine kinase activity enablesIMP 13506268PMID:17526495ARUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Fyn  (FYN proto-oncogene, Src family tyrosine kinase)
Grin1  (glutamate ionotropic receptor NMDA type subunit 1)
Grin2b  (glutamate ionotropic receptor NMDA type subunit 2B)

Objects referenced in this article
Gene Dlg3 discs large MAGUK scaffold protein 3 Rattus norvegicus
Gene Dlg4 discs large MAGUK scaffold protein 4 Rattus norvegicus

Additional Information