Studies on the phosphorylation-mediated regulation of neural morphogenesis and its involvement in hydrocephalus

2011 Fiscal Year Final Research Report

• Project/Area Number: 21680033
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: NAKAZAWA Takanobu 東京大学, 大学院・医学系研究科, 特任講師 (00447335)
• Project Period (FY): 2009 – 2011
• Keywords: Fyn / RhoGAP / チロシンリン酸化 / シグナル伝達 / 水頭症 / 神経細胞

Research Abstract

To make clear the molecular mechanisms of Fyn tyrosine kinase-mediated regulation of neural morphogenesis, I focused on TCGAP, one of Fyn substrates in the central nervous system. By analyzing TCGAP KO mice, I found that TCGAP regulated intracellular trafficking, spine morphogenesis, and dendrite morphogenesis. Together with the finding that TCGAP KO mice showed several behavioral abnormalities, Fyn-mediated phosphorylation of their substrates including TCGAP and p250GAP is necessary for higher brain functions.

Research Products

• [Journal Article] Metaplasticity gated through differential regulation of GluN2A versus GluN2B receptors by Src family kinases (2012)
  • Author(s): Yang K, Trepanier C, Sidhu B, Xie YF, Li H, Lei G, Salter MW, Nakazawa T, Yamamoto T, Jackson MF, MacDonald JF
  • Journal Title: EMBO J Volume: 31 Pages: 805-816
  • DOI: DOI:10.1038/emboj.2011.453
  • Peer Reviewed
• [Journal Article] NYAP : a phosphoprotein family that links PI3K to WAVE1 signaling in neurons (2011)
  • Author(s): Yokoyama K, Tezuka T, Kotani M, Nakazawa T, Hoshina N, Shimoda Y, Kakuta S, Sudo K, Watanabe K, Iwakura Y, Yamamoto T
  • Journal Title: EMBO J Volume: 30 Pages: 4739-4754
  • DOI: DOI:10.1038/emboj.2011.348
  • Peer Reviewed
• [Journal Article] Distinct expression patterns of the subunits of the CCR4-NOT deadenylase complex during neural development (2011)
  • Author(s): Chen C, Ito K, Takahashi A, Wang G, Suzuki T, Nakazawa T, Yamamoto T, Yokoyama K
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 411 Pages: 360-364
  • DOI: DOI:10.1016/j.bbrc.2011.06.148
  • Peer Reviewed
• [Journal Article] Involvement of spinal phosphorylation cascade of Tyr1472-NR2B, Thr286-CaMKII, and Ser831-GluR1 in neuropathic pain (2011)
  • Author(s): Katano T, Nakazawa T, Nakatsuka T, Watanabe M, Yamamoto T, Ito S
  • Journal Title: Neuropharmacol Volume: 60 Pages: 609-616
  • DOI: DOI:10.1016/j.neuropharm.2010.12.005
  • Peer Reviewed
• [Journal Article] NMDAR2B tyrosine phosphorylation modulates anxiety-like behavior by regulating CRF expression (2010)
  • Author(s): Delawary M, Tezuka T, Kiyama Y, Yokoyama K, Inoue T, Hattori S, Hashimoto R, Umemori H, Manabe T, Yamamoto T, Nakazawa T
  • Journal Title: Mol. Brain Volume: 3 Pages: 37
  • DOI: DOI:10.1186/1756-6606-3-37
• [Journal Article] Impairment of CaMKII activation and neuropathic pain in mice lacking NR2B phosphorylation at Tyr-1472 (2010)
  • Author(s): Matsumura S, Kunori S, Mabuchi T, Katano T, Abe T, Nakazawa T, Yamamoto T, Ashitaka-Okuda E, Ito S
  • Journal Title: Eur J. Neurosci Volume: 32 Pages: 798-810
  • DOI: DOI:10.1111/j.1460-9568.2010.07348.x
  • Peer Reviewed
• [Journal Article] Receptor tyrosine phosphatase sigma(RPTPsigma) regulates, p250GAP, a novel substrate that attenuates Rac signaling (2010)
  • Author(s): Chagnon MJ, Wu CL, Nakazawa T, Yamamoto T, Noda M, Blanchetot C, Tremblay ML
  • Journal Title: Cell. Signal Volume: 22 Pages: 1626-1633
  • DOI: DOI:10.1016/j.cellsig.2010.06.001
  • Peer Reviewed
• [Journal Article] Involvement of NMDAR2A tyrosine phosphorylation in depression-related behavior (2009)
  • Author(s): Taniguchi S, Nakazawa T, Tanimura A, Kiyama Y, Tezuka T, Watabe AM, Katayama N, Yokoyama K, Inoue T, Izumi-akaseko H, Kakuta S, Sudo K, Iwakura Y, Umemori H, Inoue T, Murphy PN, Hashimoto K, Kano M, Manabe T, Yamamoto, T
  • Journal Title: EMBO J Volume: 28 Pages: 3717-3729
  • DOI: DOI:10.1038/emboj.2009.300
  • Peer Reviewed
• [Presentation] A role of protocadherin 17 in presynaptic assembly of cortico-basal ganglia circuit neurons (2011)
  • Author(s): Hoshina N, Tanimura A, Yamasaki M, Inoue T, Yokoyama K, Watanabe M, Kano M, Nakazawa T, Yamamoto T
  • Organizer: 第34回日本分子生物学会・年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-13
• [Presentation] The activation of NR2B-NMDAR by phosphorylation of Tyr1472-NR2B triggers phosphorylation cascade in neuropathic pain (2011)
  • Author(s): Katano T, Nakazawa T, Nakatsuka T, Watanabe M, Yamamoto T, Ito S
  • Organizer: 41th ANNUAL MEETING Society for Neuroscience
  • Place of Presentation: Washington DC,アメリカ合衆国
  • Year and Date: 2011-11-16
• [Presentation] プロテオミクス解析による神経障害性疼痛機能性分子の探索 (2011)
  • Author(s): 片野泰代、高尾敏文、奥村宣明、中澤敬信、山本雅、伊藤誠二
  • Organizer: 第84回日本生化学会・大会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2011-09-23
• [Presentation] Dopamine and tyrosine phosphorylation of NR2B(Y1472) in the hippocampus is fundamental for ERK2 activation and novel learning (2011)
  • Author(s): David O, Nakazawa T, Yamamoto T, Rosenblum K
  • Organizer: ISN-ESN 2011
  • Place of Presentation: Athenes,ギリシャ
  • Year and Date: 2011-08-30
• [Presentation] Essential role of tyrosine phosphorylation of the NMDA receptor in mouse behavior (2011)
  • Author(s): Nakazawa T
  • Organizer: ISN-ESN 2011
  • Place of Presentation: Athenes,ギリシャ
  • Year and Date: 2011-08-30
• [Presentation] Characterization of transmembrane kinase BREK/LMTK2 in endocytic membrane trafficking (2010)
  • Author(s): Inoue T, Kawa S, Nakazawa T, Sutoh K, Yamamoto T
  • Organizer: 第33回日本分子生物学会・年会
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-12-08
• [Presentation] The role of 2-protocadherin family in synapse formation in the basal ganglia (2010)
  • Author(s): Hoshina N, Inoue T, Yokoyama K, Nakazawa T, Yamamoto T
  • Organizer: 第33回日本分子生物学会・年会
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] 神経因性疼痛における脊髄後角でのリン酸化シグナルカスケード (2010)
  • Author(s): 片野泰代、中澤敬信、渡辺雅彦、山本雅、伊藤誠二
  • Organizer: 第33回日本分子生物学会・年会
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] Attenuation of neuropathic pain by impaired Ca2+ signaling in mutant mice lacking the Tyr-1472 phosphorylation site of the NR2B (2010)
  • Author(s): Matsumura S, Kunori S, Nakazawa T, Abe T, Yamamoto T, Katano T, Watanabe M, Okuda-Ashitaka S
  • Organizer: 40th ANNUAL MEETING Society for Neuroscience
  • Place of Presentation: San Diego,アメリカ合衆国
  • Year and Date: 2010-11-15
• [Presentation] Involvement of GluN2A tyrosine phosphorylation in depression-related behavior (2010)
  • Author(s): Nakazawa T, Taniguchi S, Tanimura A, Kiyama Y, Tezuka T, Kano M, Manabe T, Yamamoto T
  • Organizer: 7th Forum of European Neuroscience(FENS)
  • Place of Presentation: Amsterdam,オランダ
  • Year and Date: 2010-07-05
• [Presentation] 小脳プルキンエ細胞GluR2細胞内プールの樹状突起スパインからシャフトへの活動依存的移動の蛍光蛋白質2重発現法による解析 (2010)
  • Author(s): 山口和彦、清水知佳、中澤敬信、伊藤正男
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡市民文化ホール(岩手県)
  • Year and Date: 2010-05-19
• [Presentation] Involvement of NMDAR2A tyrosine phosphorylation in depression-related behavior (2009)
  • Author(s): 中澤敬信、谷口幸子、谷村あさみ、城山優治、手塚徹、狩野方伸、真鍋俊也、山本雅
  • Organizer: 第32回日本分子生物学会・年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-12-12
• [Presentation] The novel NYAP phosphoprotein family couples activation of phosphoinositide 3-kinase(PI3K) p85 with the cytoskeletal WAVE signaling pathway in the brain (2009)
  • Author(s): 横山一剛、手塚徹、小谷政晴、中澤敬信、星名直祐、井上毅、霜田靖、角田茂、須藤カツ子、渡邉和忠、岩倉洋一郎、山本雅
  • Organizer: 第32回日本分子生物学会・年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-12-11