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シナプス活動による遺伝子発現の制御

Research Project

Project/Area Number 12053235
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo (2003-2004)
Kyoto University (2000-2002)

Principal Investigator

尾藤 晴彦  東京大学, 大学院・医学系研究科, 助教授 (00291964)

Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥54,500,000 (Direct Cost: ¥54,500,000)
Fiscal Year 2004: ¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 2003: ¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 2002: ¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2001: ¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 2000: ¥10,800,000 (Direct Cost: ¥10,800,000)
Keywordsカルシウム / シナプス / PSD / 遺伝子発現 / CREB / CaMK / ファルネシル化 / 脂質修飾 / 海馬 / calcium / actin / 神経活動依存性 / 形態可塑性 / CaMキナーゼ / リン酸化 / Rho / Ca2+チャンネル / 海馬錐体細胞 / 小脳顆粒細胞 / 生存 / CaMKIV / イメージング
Research Abstract

これまでCREB転写活性を修飾する脳特異的キナーゼ遺伝子CLICK-I,-II,-IIIを単離してきたが、その機能解析を次のように行っている。
1.個体レベルの解析:遺伝子欠損マウスの作成
CLICK-I,-II,-IIIのキナーゼ領域を欠損するマウスの作成のため、ES細胞において、相同遺伝子組み換えによるキナーゼ含有エキソンの破壊を行った。CLICK-IIIについては、キメラマウスを作成し、現在germline transmissionの確認中である。
2.キナーゼ変異体を用いた細胞レベルの解析
CLICK-I,-II,-IIIのキナーゼ変異体(dominant active型、kinase dead型)の表現型を、初代培養海馬錐体細胞、海馬スライスカルチャーに導入し、定量的表現型解析を現在実行中である。
またCREB標的遺伝子産物Arcに着目して神経細胞内動態の可視化を試みた。可塑性刺激様なカルシウム上昇を伴う刺激を付与した後、新規蛋白合成依存的にArcの樹状突起スパイン内発現が60〜120分以内に上昇することを発見した。また、Arcと結合する蛋白のスクリーニングよりPSD内結合蛋白を同定した。引き続き、ランダムCFP/YFP挿入法を用い、Arcとその結合蛋白の各々について、結合能を損なわないFRET対を作成・最適化し、神経細胞に遺伝子導入したところ、生きた神経細胞においてもスパイン内で、Arcとその結合蛋白の間のFRETが確認された。

Report

(5 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (21 results)

All 2004 Other

All Journal Article (1 results) Publications (20 results)

  • [Journal Article] シナプス活動による遺伝子発現制御2004

    • Author(s)
      奥野浩行, 竹本-木村さやか, 大前彰吾, 岡村理子, 石原奈津実, 尾藤晴彦
    • Journal Title

      蛋白質核酸酵素 49

      Pages: 411-418

    • Related Report
      2004 Annual Research Report
  • [Publications] Takemoto-Kimura S.et al.: "Molecular cloning and characterization of CLICK-III/CaMKIg, a novel membrane-anchored neuronal CaMK"J.Biol.Chem.. 278. 18597-18605 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuoka Y.et al.: "Impaired ACTH response to bacterial lipopolysaccharide in mice deficient in prostaglandin E receptor EP1 and EP3 subtypes"Proc.Nat.Acad.Sci.USA. 100. 4132-4137 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bito H, Takemoto-Kimura S.: "Ca2+/CREB/CBP-dependent gene regulation : a shared mechanism critical in long-term synaptic plasticity and neuronal survival"Cell Calcium. 34. 425-430 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 奥野浩行 他: "シナプス活動による遺伝子発現制御"蛋白質核酸酵素. 49. 411-418 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Furuyashiki T. et al.: "Multiple spatiotemporal modes of actin reorganization by NMDA receptors and voltage-gated Ca^<2+>-channels"Proc.Natl.Acad.Sci. USA. 99. 14458-14463 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Bito et al.: "Protocol for primary culture of mouse hippocampal pyramidal neurons"Jikken-Igaku. 20. 2247-2252 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arakawa Y, Bito H: "Rho/ROCK and neuronal cell morphology"Bio Clinica. 17. 1154-1158 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Bito H.: "CREB function in the central nervous system : control of long-term memory and apoptosis"Igaku no Ayumi. 203. 538-540 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arakawa Y, et al.: "Control of axon elongation via an SDF-1a/Rho/mDia pathway in cultured cerebellar granule neurons"J. Cell Biol.. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuoka Y: "Impaired adrenocorticotropic hormone response to bacterial bacterial endotoxin in mice deficient in prostaglandin E receptor EP1 and EP3"Proc.Natl.Acad.Sci. USA. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Takemoto-Kimura S., et al.: "Molecular characteriation of CaMK-Like CREB kinase (CLICK)-III, a novel membrane anchored Ca2+/calmodulin-dependent protein kinase (CaMK)"J.Biol.Chem.. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Furuyashiki T., et al.: "Multiple modes of activity-dependent neuronal actin reorganization in "New frontiers in biological imaging"(Kusumi, Kobayashi, Yoshimura, Tokunaga, eds"Jikken-Igaku. 32-36 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 古屋敷智之, 成宮周, 尾藤晴彦: "神経細胞におけるアクチン細胞骨格系の制御。In「神経ネットワークとシナプスのダイナミクス」"金芳堂(印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamamoto M, Hilgemann DH, Feng S, Bito H, Ishihara H, Shibasaki Y, Yin HL.: "Phosphatidylinositol 4,5-bisphosphate induces actin stress fiber formation and inhibits membrane ruffling in CV1 cells"J.Cell Biol. 152. 867-876 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamasaki T, Kawaji K, Ono K, Bito H, Hirano T, Osumi N, Kengaku M: "Pax6 regulates granule cell polarization during parallel fiber formation in the developing cerebellum"Development. 128. 3133-3144 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 古屋敷 智之, 尾藤晴彦, 成宮周: "Rhoと細胞骨格制御 in シグナル伝達:細胞運命と細胞機能を制御する仕組み"西田栄介, 大野茂男編, 共立出版. 49-67 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Bito et al.: "A critical role for a Rho-associated kinase p160ROCK in determining axon outgrowth in mammalian CNS neurons."Neuron. 26. 431-441 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mermelstein,Bito et al.: "Critical dependence of CREB phosphorylation on L-type calcium channels supports a selective response to EPSPs rather than action potentials."J.Neurosci.. 20. 266-273 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] See,Boutillier,Bito et al.: "Calcium-calmodulin dependent protein kinase type IV (CaMKIV) inhibits apoptosis induced by potassium deprivation in cerebellar granule cells."FASEB J.. 15. 134-144 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Bito et al.: "Challenges for Neuroscience in the 21st Century (Osamu Hayishi ed.)"Japan Scientific Societies Press. 107-120 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2018-03-28  

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