Regulation and de-regulation of NMDA receptor-dependent synaptic plasticity through its tyrosine phosphorylation

• Project/Area Number: 19390070
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: YAMAMOTO Tadashi The University of Tokyo, 医科学研究所, 教授 (40134621)
• Co-Investigator(Renkei-kenkyūsha): NAKAZAWA Takanobu 東京大学, 医科学研究所, 助教 (00447335)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2008: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000); Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: 脳 / 神経 / 神経科学 / Src型キナーゼ / NMDA受容体 / チロシンリン酸化 / 遺伝子改変マウス / 行動実験 / チャネル活性 / 線条体 / プロテオミクス / 2D-DIGE

Research Abstract

NMDA受容体は、イオンチャネルであると共に、細胞内シグナル分子でもある。私はNMDA受容体構成成分であるNR2A, 2Bのチロシンリン酸化がNMDA受容体の機能や作用の制御に関わると提唱してきた。本研究では、NMDA受容体のチロシンリン酸化部位を改変した遺伝子操作マウスを用い、NR2AやNR2Bのチロシンリン酸化が、それぞれ線条体でのドーパミンニューロンの活性化や扁桃でのLTP誘導を制御し、マウスの抗鬱反応や恐怖学習に関与することを示した。

Research Products

• [Journal Article] Activation of Fyn tyrosine kinase in the mouse dorsal hippocampus is essential for contextual fear conditioning (2008)
  • Author(s): Isosaka T, Hattori K, Kida S, Kohno T, Nakazawa T, Yamamoto T, Yagi T and Yuasa S
  • Journal Title: Eur J Neurosci 28 Pages: 973-981
  • Peer Reviewed
• [Journal Article] Regulation of dendritic spine morphology by an NMDA receptor-associated Rho GTPase-activating protein, p250GAP. J. (2008)
  • Author(s): Nakazawa T, Kuriu T, Tezuka T, Umemori H, Okabe S, and Yamamoto T,
  • Journal Title: Neurochem 105 Pages: 1384-1393
  • Peer Reviewed
• [Journal Article] Loss of Fyn tyrosine kinase on the C57BL/6 genetic background causes hydrocephalus with defects in oligodendrocyte development. (2008)
  • Author(s): Goto J, Tezuka T, Nakazawa T, Sagara H, and Yamamoto T.
  • Journal Title: Mol Cell Neurosci 38 Pages: 203-212
  • Peer Reviewed
• [Journal Article] Activation of Fyn tyrosine kinase in the mouse dorsal hippocampus is essential for contextual fear conditioning (2008)
  • Author(s): Isosaka T et al
  • Journal Title: Eur.J. Neurosci. 28 Pages: 973-981
  • Peer Reviewed
• [Journal Article] Regulation of dendritic spine morphology by an NMDA receptor-associated Rho GTPase-activating protein, p250GAP. (2008)
  • Author(s): Nakazawa T et al
  • Journal Title: J. Neurochem. 105 Pages: 1384-1393
  • Peer Reviewed
• [Journal Article] Loss of Fyn tyrosine kinase on the C57BL/6 genetic background causes hydrocephalus with defects in oligodendrocyte development. (2008)
  • Author(s): Goto J et al
  • Journal Title: Mol. Cell. Neurosci. 38 Pages: 203-212
  • Peer Reviewed
• [Journal Article] Kid-mediated chromosome compaction ensures proper nuclear envelop formation. (2008)
  • Author(s): Ohsugi M et al
  • Journal Title: Cell 132 Pages: 771-782
  • Peer Reviewed
• [Journal Article] Ajuba negatively regulates the Wnt signaling pathway by promoting GSK-3β-mediated phosphorylation of β -catenin. (2008)
  • Author(s): Haraguchi K et al
  • Journal Title: Oncogene 27 Pages: 274-284
  • Peer Reviewed
• [Journal Article] Regulation of dendritic spine morphology by ab NMDAreceptor-associted Rho GTPase-activating protein, p250GAP (2008)
  • Author(s): Nakazawa T, et. al.
  • Journal Title: J. Neuochem 105 Pages: 1384-1393
  • Peer Reviewed
• [Journal Article] Involvement of protein-tyrosine phosphatase PTPMEG in motor learning and cerebellar long-term depression (2007)
  • Author(s): Kina S, Tezuka T, Kusakawa S, Kishimoto Y, Kakizawa S, Hashimoto K, Ohsugi M, Kiyama Y, Horai R, Sudo K, Kakuta S, Iwakura Y, Iino M, Kano M, Manabe T, Yamamoto T
  • Journal Title: Eur J Neurosci 26 Pages: 2269-2278
  • Peer Reviewed
• [Journal Article] Focal adhesion kinase regulates laminin-induced oligodendroglial process outgrowth (2007)
  • Author(s): Hoshina N, Tezuka T, Yokoyama K, Kozuka-Hata H, Oyama M and Yamamoto T
  • Journal Title: Genes to Cells 12 Pages: 1245-1254
  • Peer Reviewed
• [Journal Article] Neurotensin type 2 receptor in astrocytes is involved in fear memory in mice (2007)
  • Author(s): Yamaguchi R, Wada E, Kamichi S, Yamada D, Maeno H, Delawary M, Nakazawa T, Yamamoto T, and Wada K
  • Journal Title: J. Neurochem 102 Pages: 1669-1676
  • Peer Reviewed
• [Journal Article] ZRP-1 controls Rho GTPase-mediated actin reorganization by localizing at cell-matrix and cell-cell adhesions (2007)
  • Author(s): Delawary M, Nakazawa T, Tezuka T, Sawa M, Iino Y, Takenawa T, and Yamamoto T
  • Journal Title: J. Cell Sci 120 Pages: 2828-2837
  • Peer Reviewed
• [Journal Article] Molecular characterization of a novel RhoGAP, RRC-1 of the nematode Caenorhabditis elegans. Biochem (2007)
  • Author(s): Chikamori M, Fujimoto J, Tokai-Nishizumi N, and Yamamoto T.
  • Journal Title: Biophys. Res. Commun 357 Pages: 377-82
  • Peer Reviewed
• [Journal Article] Identification of multiple SNT-binding sites on NPM-ALK oncoprotein and their involvement in cell transformation (2007)
  • Author(s): Chikamori M, Fujimoto J, Tokai-Nishizumi N, Yamamoto T.
  • Journal Title: Oncogene 26 Pages: 2950-2954
  • Peer Reviewed
• [Journal Article] Involvement of protein-tyosine phophatase PTPMEG in motor learing and cerebrllar long-term depression (2007)
  • Author(s): Kina S, et. al.
  • Journal Title: Eur J Neurosci 26(8) Pages: 2269-2278
  • Peer Reviewed
• [Journal Article] Focal adhesion kinase regulates laminin-induced oligodendroglial process outgrowth (2007)
  • Author(s): Hoshina N, et. al.
  • Journal Title: Genes to Cells 12 Pages: 1245-1254
  • Peer Reviewed
• [Journal Article] Neurotensin type 2 receptor in astrocytes is involved in fear memory in mice (2007)
  • Author(s): Yamaguchi R, et. al.
  • Journal Title: J. Neurochem 102 Pages: 1669-1676
  • Peer Reviewed
• [Journal Article] Diversity of translation start sites define increeased complecxity of human short ORFeom (2007)
  • Author(s): Oyama M, et. al.
  • Journal Title: Mol. Cell. Proteomics 6 Pages: 1000-1006
  • Peer Reviewed
• [Journal Article] Molecular characterization of a novel RhoGAP, RRC-1 of the nematode Canorhabditis elegans (2007)
  • Author(s): Delawary M, et. al.
  • Journal Title: Biochem, Biophys. Res. Commun 357 Pages: 177-382
  • Peer Reviewed
• [Journal Article] Identification of multiple SNT-binding sites on NPM-ALK oncoprotein and the irinvolvement in cell transformation (2007)
  • Author(s): Chikamori M, et. al.
  • Journal Title: 0ncogene 26 Pages: 2950-2954
  • Peer Reviewed
• [Presentation] Characterization of transmembrane kinase BREK/LMTK2 in endocytic membrane trafficking (2008)
  • Author(s): 井上毅ら
  • Organizer: 第31回日本分子生物学会大会(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] 中枢神経系における新規プロトカドへリンを介したシグナル伝達機構の解析 (2008)
  • Author(s): 星名直祐(山本雅)
  • Organizer: 第31回日本分子生物学会年会(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Characterization of transmembrane kinase BREK/LMTK2 in endocytic membrane trafficking (2008)
  • Author(s): 井上毅(山本雅)
  • Organizer: 第31回日本分子生物学会年会(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] NYAPファミリーは神経細胞特異的に発言するPI3-kinase p85の主要な制御因子である (2008)
  • Author(s): 横山一剛(山本雅)
  • Organizer: 第31回日本分子生物学会年会(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] 中枢神経系における新規プロトカドヘリンを介したシグナル伝達機構の解析 (2008)
  • Author(s): 星名直祐ら
  • Organizer: 第31回日本分子生物学会大会(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Involvement of phosphorylation of NR2B subunit of NMDA receptor at Tyr1472 in maintenance of neuroPathic pain (2008)
  • Author(s): Ito S et al
  • Organizer: 12th World Congress of Pain
  • Place of Presentation: Glasgow
• [Presentation] p250GAP, a brain-enriched RhoGAP, in involved in the NMDAR-mediated signaling (2008)
  • Author(s): 中澤敬信ら
  • Organizer: 第31回日本神経科学学会大会(Neuro2008)
  • Place of Presentation: 東京
• [Presentation] Involvement of NR2A tyrbsine phosphorylation in depression-related behaviors (2008)
  • Author(s): 手塚徹ら
  • Organizer: 第31回日本神経科学学会大会(Neuro2008)
  • Place of Presentation: 東京
• [Presentation] Cblファミリー蛋白質による表皮形成制御 (2007)
  • Author(s): 手塚徹(山本雅)
  • Organizer: 第30回日本分子生物学会年会(BMB2007)
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] NMDA受容体チロシンリン酸化による脳高次機能制御 (2007)
  • Author(s): 中澤 敬信、山本 雅
  • Organizer: 第30回日本分子生物学会年会(BMB2007)(ワークショッナ)
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] オリゴデンドロサイトの突起伸長におけるFAKの機能解析 (2007)
  • Author(s): 星名直祐(山本雅)
  • Organizer: 第30回日本分子生物学会年会(BMB2007)
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] Phosphorylation at Tyr-694 of Nogo-A by Src-family kinases (2007)
  • Author(s): 横山一剛(山本雅)
  • Organizer: 第30回日本分子生物学会年会(BMB2007)
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] ユビキチン連結酵素Cbl-cのX線結晶構造解析による標的基礎認識機構の研究 (2007)
  • Author(s): 手塚徹(中川敦史)
  • Organizer: 第30回日本分子生物学会年会(BMB2007)
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] Human PTPMEGのX線結晶構造解析を目的とした大量発現系の構築 (2007)
  • Author(s): 手塚徹(中川敦史)
  • Organizer: 第30回日本分子生物学会年会(BMB2007)
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] Regulation of dendritic spin morphology by an NMDA receptor-associated RhoGAP, p250GAP (2007)
  • Author(s): 中澤敬信(山本雅)
  • Organizer: NEUROSCIENCE 2007
  • Place of Presentation: サンディエゴ
  • Year and Date: 2007-11-06
• [Presentation] Regulation of dendritic spine morphology by an NMDA receptor-associated RhoGAP, p250GAP (2007)
  • Author(s): Nakazawa T, Kuriu T, Okabe S, Yamamoto
  • Organizer: 37th ANNUAL MEETING Society for Neuroscience
  • Place of Presentation: San Diego
  • Year and Date: 2007-11-06
• [Presentation] Regulation of amygdala fUnctions by NMDAR tyrosine phosphorylation (2007)
  • Author(s): 中澤 敬信、デラワリミナ、山本 雅
  • Organizer: 第30回日本神経科学学会木会(Neuro2007)
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-10