NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity.
Phosphorylation of neural proteins in response to a diverse array of external stimuli is one of the main mechanisms underlying dynamic changes in neural circuitry. The NR2B subunit of the NMDA receptor is tyrosine-phosphorylated in the brain, with Tyr-1472 its major phosphorylation site. Here, we generate mice with a knockin mutation of the Tyr-1472 site to phenylalanine (Y1472F) and show that Tyr-1472 phosphorylation is essential for fear learning and amygdaloid synaptic plasticity. The knockin mice show impaired fear-related learning and reduced amygdaloid long-term potentiation. NMDA receptor-mediated CaMKII signaling is impaired in YF/YF mice. Electron microscopic analyses reveal that the Y1472F mutant of the NR2B subunit shows improper localization at synapses in the amygdala. We thus identify Tyr-1472 phosphorylation as a key mediator of fear learning and amygdaloid synaptic plasticity.
Nakazawa
Takanobu
T
Division of Oncology, Department of Cancer Biology, University of Tokyo, Tokyo, Japan.
Komai
Shoji
S
Watabe
Ayako M
AM
Kiyama
Yuji
Y
Fukaya
Masahiro
M
Arima-Yoshida
Fumiko
F
Horai
Reiko
R
Sudo
Katsuko
K
Ebine
Kazumi
K
Delawary
Mina
M
Goto
June
J
Umemori
Hisashi
H
Tezuka
Tohru
T
Iwakura
Yoichiro
Y
Watanabe
Masahiko
M
Yamamoto
Tadashi
T
Manabe
Toshiya
T
D000679:Amygdala / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003214:Conditioning, Classical; D005239:Fear / Q000502:physiology*; D007858:Learning / Q000502:physiology; D051379:Mice; D009154:Mutation / Q000235:genetics; D009473:Neuronal Plasticity; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D021381:Protein Transport; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism* / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission; D013746:Tetany
C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D019000:Phosphotyrosine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases