[Regulation of NMDA receptor function by Fyn-mediated tyrosine phosphorylation].
The ionnotropic glutamate receptor, N-methyl-D-aspartate (NMDA) receptor, is a prominent ligand-gated and voltage-gated ion channel in excitatory synaptic transmission in the mammalian central nervous system. The NMDA channel is also regulated by its phosphorylation. We have shown that an Src family kinase Fyn phosphorylates NR2A and NR2B subunits of the NMDA receptor. The phosphorylation events are facilitated by the presence of PSD-95, which is quite likely due to the complex formation of Fyn, PSD-95, and the NMDA receptor: Fyn interacts with PSD-95 and PSD-95 interacts with the NMDA receptor. We have identified tyrosine phosphorylation sites on NR2A and NR2B. A phosphorylation of one of the sites on NR2B (Tyr1472) is largely dependent on Fyn and is elevated upon the LTP induction of hippocampal CA1 neurons. The data suggest that Tyr-1472 phosphorylation of NR2B is important for synaptic plasticity. A phosphorylation of the other tyrosine residues of NR2A and NR2B would also be involved in brain development and function.
Nakazawa
Takanobu
T
Division of Oncology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639 Japan.
Tezuka
Tohru
T
Yamamoto
Tadashi
T
D000818:Animals; D006801:Humans; D009419:Nerve Tissue Proteins / Q000502:physiology; D009473:Neuronal Plasticity; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051076:Proto-Oncogene Proteins c-fyn; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins; D014443:Tyrosine; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn