title: NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity.
abstract: 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.
authors.affiliation: Division of Oncology, Department of Cancer Biology, University of Tokyo, Tokyo, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Shoji
authors.initials: S
authors.lastname: Komai
authors.forename: Ayako M
authors.initials: AM
authors.lastname: Watabe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kiyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukaya
authors.forename: Fumiko
authors.initials: F
authors.lastname: Arima-Yoshida
authors.forename: Reiko
authors.initials: R
authors.lastname: Horai
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ebine
authors.forename: Mina
authors.initials: M
authors.lastname: Delawary
authors.forename: June
authors.initials: J
authors.lastname: Goto
authors.forename: Hisashi
authors.initials: H
authors.lastname: Umemori
authors.forename: Tohru
authors.initials: T
authors.lastname: Tezuka
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Toshiya
authors.initials: T
authors.lastname: Manabe
mesh_terms: 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
chemical_list: 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