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Regulatory mechanism for spine morphogenesis by a small G-protein Rheb

Research Project

Project/Area Number 21500332
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionTokyo Metropolitan Organization for Medical Research

Principal Investigator

SUGIURA Hiroko  公益財団法人東京都医学総合研究所, 基盤技術研究センター, 基盤技術研究職員 (40162870)

Co-Investigator(Kenkyū-buntansha) TANAKA Hidekazu  大阪大学, 医学系研究科, 准教授 (70273638)
Co-Investigator(Renkei-kenkyūsha) KATSURABAYASHI Shutaro  福岡大学, 薬学部, 助教 (50435145)
Project Period (FY) 2009 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsスパイン / Rheb / rheb / 自閉症 / 結節性硬化症 / ミトコンドリア / ATP / ラパマイシン / 樹状突起
Research Abstract

An activity-regulated small G-protein Rheb is activated in tuberous sclerosis, which is accompanied with dendritic spine dysmorphogenesis. We have investigated the underlying mechanism and have clarified that mitochondria is increased in dendrites of tuberous sclerosis neurons and that impaired spinogenesis in tuberous sclerosis is caused by an increase in RBP levels, not due to mTORC1 activation. These findings may lead to development of a new treatment for tuberous sclerosis associated with epilepsy, mental retardation or autism.

Report

(5 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (48 results)

All 2012 2011 2010 2009 Other

All Journal Article (16 results) (of which Peer Reviewed: 14 results) Presentation (24 results) Book (6 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] 過剰興奮によって生じるシナプス減少のメカニズム2012

    • Author(s)
      安田新、杉浦弘子、山形要人
    • Journal Title

      日本薬理学雑誌

      Volume: 140 Pages: 141-141

    • URL

      http://plaza.umin.ac.jp/JPS1927/fpj/issue/TOC12-140%283%29/12-140-3.htm

    • Related Report
      2012 Final Research Report
  • [Journal Article] 過剰興奮後に生じるスパインが減少するメカニズム2012

    • Author(s)
      安田新
    • Journal Title

      日本薬理学雑誌

      Volume: 140 Pages: 141-141

    • Related Report
      2012 Annual Research Report
  • [Journal Article] p38 MAP kinase inhibitors as potential therapeutic drugs for neural diseases2011

    • Author(s)
      Yasuda S, Sugiura H, Tanaka H, Takigami S, Yamagata K
    • Journal Title

      Cent Nerv Syst Agents Med Chem

      Volume: 11(1) Pages: 45-59

    • URL

      http://www.eurekaselect.com/87633/article

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial microsomal prostaglandin E synthase-1 facilitates neurotoxicity by elevating astrocytic Ca2+ levels2011

    • Author(s)
      Takemiya T, Matsumura K, Sugiura H, Yasuda S, Uematsu S, Akira S, Yamagata K
    • Journal Title

      Neurochem Int

      Volume: 58 Issue: 4 Pages: 489-496

    • DOI

      10.1016/j.neuint.2011.01.003

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Retrospective review of Japanese sudden unexpected death in infancy : the importance of metabolic autopsy and expanded newborn screening.2011

    • Author(s)
      Yamamoto T, et al.
    • Journal Title

      Mol Genet Metab

      Volume: In press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial microsomal prostaglandin E synthase-1 exacerbates neuronal loss induced by kainate2010

    • Author(s)
      Takemiya T, Matsumura K, Sugiura H, Maehara M, Yasuda S, Uematsu S, Akira S, Yamagata K
    • Journal Title

      J Neurosci Res

      Volume: 88(2) Issue: 2 Pages: 381-90

    • DOI

      10.1002/jnr.22195

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial microsomal prostaglandin E synthase-1 facilitates neurotoxicity by elevating astrocytic Ca(2+) levels.2010

    • Author(s)
      Takemiya T, et al.
    • Journal Title

      Neurochem Int

      Volume: In press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel transporter of SLC22 family specifically transports prostaglandins and co-localizes with 15-hydroxyprostaglandin dehydrogenase in renal proximal tubules.2010

    • Author(s)
      Shiraya K, et al.
    • Journal Title

      J Biol Chem.

      Volume: 285 Pages: 22141-22151

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p38 Map Kinase Inhibitors as Potential Therapeutic Drugs for Neural Diseases.2010

    • Author(s)
      Yasuda S, et al.
    • Journal Title

      Cent Nerv Syst Agents Med Chem.

      Volume: In press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial microsomal prostaglandin E synthase-1 exacerbates neuronal loss induced by kainate2010

    • Author(s)
      Takemiya T, et al.
    • Journal Title

      J Neurosci Res 88(2)

      Pages: 381-90

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p38 MAP kinase inhibitors as potential therapeutic drugs for neural diseases2010

    • Author(s)
      Yasuda S, et al.
    • Journal Title

      Curr.Med.Chem.CNS Agents (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transducing neuronal activity into dendritic spine morphology: new roles for p38 MAP kinase and N-cadherin2009

    • Author(s)
      Sugiura H, Tanaka H, Yasuda S, Takemiya T, Yamagata K
    • Journal Title

      Neuroscientist

      Volume: 15(1) Issue: 1 Pages: 90-104

    • DOI

      10.1177/1073858408324024

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article]2009

    • Author(s)
      Mek3.Yasuda S, Sugiura H, Yamagata K
    • Journal Title

      UCSD-Nature Molecule Pages

    • DOI

      10.1038/mp.a001507.01

    • URL

      http://www.signaling-gateway.org/molecule/query?afcsid=A001507

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] N-cadherin regulates differentiation of neural precursor cells2009

    • Author(s)
      Yagita Y, et al.
    • Journal Title

      J Neurosci Res 87

      Pages: 3331-3342

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mek32009

    • Author(s)
      Yasuda, et al.
    • Journal Title

      UCSD-Nature Molecule Pages

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methanphetamine directly accelerates beating rate in cardiomyocytes by increasing Ca2+ entry via L-type Ca2+ channel2009

    • Author(s)
      Sugimoto K, et al.
    • Journal Title

      Biochem Biophys Res Commun 390

      Pages: 1214-1220

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Novel mechanism for dendritic spine abnormality in tuberous sclerosis2012

    • Author(s)
      Yasuda S, Sugiura H, Katsurabayashi S, Iwasaki K, Hino O and Yamagata K
    • Organizer
      The 11th Biennial Meeting of the Asian Pacific Society for Neurochemistry, The 55th Annual Meeting of the Japanese Society for Neurochemistry
    • Place of Presentation
      Kobe
    • Year and Date
      2012-09-30
    • Related Report
      2012 Final Research Report
  • [Presentation] 結節性硬化症におけるスパイン形成不全の分子メカニズム2012

    • Author(s)
      山形要人 杉浦弘子 安田新 桂林秀太郎 高崎浩太郎 岩崎克典 樋野興夫
    • Organizer
      第63回日本薬理学会北部会
    • Place of Presentation
      新潟
    • Year and Date
      2012-09-14
    • Related Report
      2012 Final Research Report
  • [Presentation] TSC変異モデルにみられる興奮性シナプス形成異常のメカニズム2011

    • Author(s)
      安田新、杉浦弘子、樋野興夫、山形要人
    • Organizer
      第54回日本神経化学会大会
    • Place of Presentation
      山代
    • Year and Date
      2011-09-26
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] カイニン酸刺激による樹状突起スパイン退縮の分子メカニズム2011

    • Author(s)
      安田新、杉浦弘子、竹宮孝子、田中秀和、山形要人
    • Organizer
      第34回日本神経科学学会
    • Place of Presentation
      横浜
    • Year and Date
      2011-09-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] 自閉症モデル動物における樹状突起スパイン形成異常のメカニズム2011

    • Author(s)
      安田新、杉浦弘子、樋野興夫、山形要人
    • Organizer
      第33回日本生物学的精神医学会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] 結節性硬化症における樹状突起スパイン形成異常の分子メカニズム2010

    • Author(s)
      杉浦弘子、安田新、樋野興夫、山形要人
    • Organizer
      BMB2010 第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会
    • Place of Presentation
      神戸コンベンションセンター
    • Year and Date
      2010-12-08
    • Related Report
      2012 Final Research Report
  • [Presentation] 結節性硬化症における樹状突起スパイン形成異常の分子メカニズム2010

    • Author(s)
      杉浦弘子, 他
    • Organizer
      BMB2010
    • Place of Presentation
      神戸コンベンションセンター
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] 海馬神経細胞接着分子N-cadherin結合蛋白質の網羅的解析2010

    • Author(s)
      田中秀和, 他
    • Organizer
      第118回日本薬理学会近畿部会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪府)
    • Year and Date
      2010-11-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] カイニン酸によって生じる樹状突起スパイン減少におけるp38 MAPキナーゼの役割2010

    • Author(s)
      安田新、杉浦弘子、田中秀和、竹宮孝子、山形要人
    • Organizer
      第44回 日本てんかん学会
    • Place of Presentation
      岡山コンベンションセンター「ママカリフォーラム」
    • Year and Date
      2010-10-14
    • Related Report
      2012 Final Research Report
  • [Presentation] カイニン酸によって生じる樹状突起スパイン減少におけるp38 MAPキナーゼの役割2010

    • Author(s)
      安田新, 他
    • Organizer
      第44回日本てんかん学会
    • Place of Presentation
      岡山コンベンションセンター
    • Year and Date
      2010-10-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] 結節性硬化症モデル動物における樹状突起スパイン形態異常のメカニズム2010

    • Author(s)
      安田新、杉浦弘子、樋野興夫、山形要人
    • Organizer
      Neuro2010 第33回日本神経科学大会 第53回日本神経化学会大会 第20回日本神経回路学会大会 合同大会
    • Place of Presentation
      神戸コンベンションセンター
    • Year and Date
      2010-09-02
    • Related Report
      2012 Final Research Report
  • [Presentation] 結節性硬化症モデル動物における樹状突起スパイン形態異常のメカニズム2010

    • Author(s)
      安田新, 他
    • Organizer
      Neuro2010
    • Place of Presentation
      神戸コンベンションセンター
    • Year and Date
      2010-09-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Protocadherin arcadlin regulates seizure-induced synaptic loss by activating p38 MAP kinase signaling2010

    • Author(s)
      Yasuda S, Sugiura H, Tanaka H, Takemiya T, Yamagata K
    • Organizer
      BIT Life Sciences' 3'rd Annual Protein and Peptide Conference (Pepcon)-2010
    • Place of Presentation
      Beijing, People's Republic of China
    • Year and Date
      2010-03-21
    • Related Report
      2012 Final Research Report
  • [Presentation] Protocadherin Arcadlin Regulates Seizure-induced Synaptic Loss by Activating p38 MAP Kinase Signaling2010

    • Author(s)
      Yasuda S, et al.
    • Organizer
      3'rd BIT Peptide and Protein Conference(Pepcon)-2010
    • Place of Presentation
      北京(中国)
    • Year and Date
      2010-03-21
    • Related Report
      2009 Annual Research Report
  • [Presentation] シナプス接着部分でダイナミックな働きをする蛋白質の探索2010

    • Author(s)
      田中秀和, ほか
    • Organizer
      日本薬理学会年会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-03-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] Morphological alterations of neuronal dendrites in developmental disorder model2009

    • Author(s)
      Takigami, S. Yasuda, S. Sugiura, H. Yoshimura, Y. Takemiya, T. Yamauchi, T. Hino, O. Yamagata, K
    • Organizer
      第32回日本神経科学大会
    • Place of Presentation
      愛知県名古屋市
    • Year and Date
      2009-09-18
    • Related Report
      2012 Final Research Report
  • [Presentation] Morphological alterations of neuronal dendrites in developmental disorder model2009

    • Author(s)
      瀧上周, et al.
    • Organizer
      第32回日本神経科学大会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-09-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] Dynamic roles of proteins in synaptic adherens junction2009

    • Author(s)
      田中秀和, et al.
    • Organizer
      36^<th> International congress of physiological sciences
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2009-07-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] シナプスリモデリングの情報伝達経路の探索2009

    • Author(s)
      田中秀和, ほか
    • Organizer
      日本薬理学会近畿部会
    • Place of Presentation
      石川県金沢市ホテル金沢
    • Year and Date
      2009-06-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] Electron microscopic studies on neuronal dendritic abnormality caused by TSC-2 mutation2009

    • Author(s)
      Takigami, S. Yasuda, S. Sugiura, H. Yoshimura, Y. Takemiya, T. Yamauchi, T. Hino, O. Yamagata, K
    • Organizer
      第52回日本神経化学会大会
    • Place of Presentation
      群馬
    • Year and Date
      2009-06-24
    • Related Report
      2012 Final Research Report
  • [Presentation] Electron microscopic studies on neuronal dendritic abnormality caused by TSC-2 mutation2009

    • Author(s)
      瀧上周, et al.
    • Organizer
      第52日本神経化学会大会
    • Place of Presentation
      群馬
    • Year and Date
      2009-06-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] 結節性硬化症モデルラットにおける神経細胞樹状突起の形態異常2009

    • Author(s)
      瀧上周、杉浦弘子、安田新、吉村好之、竹宮孝子、山内卓、樋野興夫、山形要人
    • Organizer
      第147回日本獣医学会学術集会
    • Place of Presentation
      栃木県総合文化センター
    • Year and Date
      2009-04-03
    • Related Report
      2012 Final Research Report 2009 Annual Research Report
  • [Presentation] Novel mechanism for dendritic spine abnormality in tuberous sclerosis

    • Author(s)
      Yasuda S
    • Organizer
      The 55th Annual Meeting of the Japanese Society for Neurochemistry
    • Place of Presentation
      Kobe
    • Related Report
      2012 Annual Research Report
  • [Presentation] 結節性硬化症におけるスパイン形成不全の分子メカニズム

    • Author(s)
      山形要人
    • Organizer
      第63回日本薬理学会北部会
    • Place of Presentation
      新潟
    • Related Report
      2012 Annual Research Report
  • [Book] Mek3. In: Encyclopedia of Signaling Molecules2012

    • Author(s)
      Yasuda S
    • Publisher
      Springer
    • Related Report
      2012 Annual Research Report
  • [Book] Encyclopedia of Signaling Molecules2012

    • Author(s)
      Yasuda S, et al.
    • Publisher
      Elsevier(掲載確定)
    • Related Report
      2010 Annual Research Report
  • [Book] Activity-dependent spine remodeling and brain disorders, in "Dendritic Spines: Biochemistry, Modeling and Properties"2009

    • Author(s)
      Takigami S, Yasuda S, Sugiura H, Tanaka H and Yamagata K
    • Publisher
      Nova science publishers, New York
    • Related Report
      2012 Final Research Report
  • [Book] Dendritic Spines : Biochemistry, Modeling and Properties2009

    • Author(s)
      Takigami S, et al.
    • Total Pages
      197
    • Publisher
      Nova Science Publishers
    • Related Report
      2009 Annual Research Report
  • [Book] Encyclopedia of Signaling Molecules

    • Author(s)
      Yasuda S, Sugiura H, Yamagata K
    • Publisher
      Mek3(in press)
    • Related Report
      2012 Final Research Report
  • [Book] Mek3 (in Encyclopedia of Signaling Molecules)

    • Author(s)
      Yasuda S, Sugiura H, Yamagata K
    • Publisher
      Springer Verlag(in press)
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] スパイン形成異常を抑制するための医薬品組成物2012

    • Inventor(s)
      山形要人 杉浦弘子 安田新
    • Industrial Property Rights Holder
      山形要人 杉浦弘子 安田新
    • Filing Date
      2012-09-07
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] スパイン形成異常を抑制するための医薬品組成物2012

    • Inventor(s)
      山形要人 杉浦弘子 安田新
    • Industrial Property Rights Holder
      山形要人 杉浦弘子 安田新
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-09-07
    • Related Report
      2012 Annual Research Report

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Published: 2009-04-01   Modified: 2019-07-29  

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