Characterization of Fyn-mediated Tyrosine Phosphorylation Sites on GluRε2 (NR2B) Subunit of theN-Methyl-d-aspartate Receptor*
By T. Nakazawa, S. Komai, T. Tezuka, C. Hisatsune, H. Umemori, K. Semba, M. Mishina, T. Manabe, Tadashi Yamamoto. Journal of Biological Chemistry, 2001
426 citations recorded by the source corpus.
The N-methyl-d-aspartate (NMDA) receptors play critical roles in synaptic plasticity, neuronal development, and excitotoxicity. Tyrosine phosphorylation of NMDA receptors by Src-family tyrosine kinases such as Fyn is implicated in synaptic plasticity. To precisely address the roles of NMDA receptor tyrosine phosphorylation, we identified Fyn-mediated phosphorylation sites on the GluRε2 (NR2B) subunit of NMDA receptors. Seven out of 25 tyrosine residues in the C-terminal cytoplasmic region of GluRε2 were phosphorylated by Fyn in vitro. Of these 7 residues, Tyr-1252, Tyr-1336, and Tyr-1472 in GluRε2 were phosphorylated in human embryonic kidney fibroblasts when co-expressed with active Fyn, and Tyr-1472 was the major phosphorylation site in this system. We then generated rabbit polyclonal antibodies specific to Tyr-1472-phosphorylated GluRε2 and showed that Tyr-1472 of GluRε2 was indeed phosphorylated in murine brain using the antibodies. Importantly, Tyr-1472 phosphorylation was greatly reduced infyn mutant mice. Moreover, Tyr-1472 phosphorylation became evident when hippocampal long term potentiation started to be observed, and its magnitude became larger in murine brain. Finally, Tyr-1472 phosphorylation was significantly enhanced after induction of long term potentiation in the hippocampal CA1 region. These data suggest that Tyr-1472 phosphorylation of GluRε2 is important for synaptic plasticity.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/d395621294d97bd5a6506c54b5d3b178e9ac368d
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Citations in the corpus
- Glutamate Receptor Ion Channels: Structure, Regulation, and Function (2010, background): “Phosphorylation of this tyrosine is eliminated in a fyn knockout (Abe et al., 2005) and is increased in hippocampal CA1 during LTP (Nakazawa et al., 2001) as well as in a chronic neuropathic pain model (Abe et al., 2005).”
- Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. (2010, positive): “Uncoupled NMDA Receptors and PSD-95 in D tau and tau (cid:1) / (cid:1) Synapses The postsynaptic NR subunit NR2b is a known substrate of Fyn (Nakazawa et al., 2001).”