Article
- The EMBO Journal (2006) 25, 2867 - 2877
- doi:10.1038/sj.emboj.7601156
Published online: 18 May 2006
Subject Category:
NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity
Takanobu Nakazawa1,a, Shoji Komai2,a, Ayako M Watabe2,a, Yuji Kiyama2, Masahiro Fukaya4, Fumiko Arima-Yoshida2, Reiko Horai3, Katsuko Sudo3, Kazumi Ebine3, Mina Delawary1, June Goto1, Hisashi Umemori1, Tohru Tezuka1, Yoichiro Iwakura3, Masahiko Watanabe4, Tadashi Yamamoto1 and Toshiya Manabe2,5
- Division of Oncology, Department of Cancer Biology, University of Tokyo, Tokyo, Japan
- Division of Neuronal Network, Department of Basic Medical Sciences, University of Tokyo, Tokyo, Japan
- Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
- Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan
- CREST, Japan Science and Technology Agency, Tokyo, Japan
Correspondence to:
Tadashi Yamamoto, Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. Tel.: +81 3 5449 5301; Fax: +81 3 5449 5413; E-mail: tyamamot@ims.u-tokyo.ac.jp
Toshiya Manabe, Division of Neuronal Network, Department of Basic Medical Sciences, University of Tokyo, Tokyo 108-8639, Japan. Tel.: +81 3 5449 5799; Fax: +81 3 5449 5794; E-mail: tmanabe-tky@umin.ac.jp
aThese authors contributed equally to this work
Received 26 September 2005; Accepted 28 April 2006
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.
Keywords:
- amygdala,
- fear learning,
- NMDA receptor,
- synaptic plasticity,
- tyrosine phosphorylation
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
Short-term plasticity at the calyx of held
Nature Reviews Neuroscience Review (01 Jan 2002)
NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders
Nature Reviews Neuroscience Review (01 Jun 2007)
NEWS AND VIEWS
LTP: AMPA receptors trading places
Nature Neuroscience News and Views (01 May 2006)
Nature Medicine News and Views (01 Dec 2008)
RESEARCH
Neurogranin enhances synaptic strength through its interaction with calmodulin
The EMBO Journal Article (07 Oct 2009)
