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Interaction of AAA chaperones with amyloid fibrils related to human diseases

Research Project

Project/Area Number 24659432
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionKumamoto University

Principal Investigator

OGURA Teru  熊本大学, 発生医学研究所, 教授 (00158825)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsAAA型シャペロン / VCP / 神経変性疾患 / TDP-43 / アミロイド線維 / 高速原子間力顕微鏡
Research Abstract

Amyloid fibrils of TDP-43 accumulate in patients of neurodegenerative diseases caused by mutations in the AAA chaperone VCP. Specific interaction of VCP with TDP-43 amyloid fibrils was demonstrated biochemically and by high-speed atomic force microscopy. Disease-related mutations reduced interaction between VCP and TDP-43 amyloid fibrils. VCP showed a significant disaggregation activity of TDP-43 amyloid fibrils in the presence of ATP. High-speed AFM analysis revealed that the N-D1 ring of CDC-48, a C. elegans VCP homolog, repeatedly rotates clockwise and resets against the D2 ring. A similar result was obtained with human VCP. Based on these observations, we have proposed that repeated back and forward rotations of VCP may account for mechanical force in disaggregation.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (33 results)

All 2014 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (17 results) (of which Invited: 2 results) Book (2 results) Remarks (9 results)

  • [Journal Article] High-speed atomic force microscopic observation of ATP-dependent rotation of the AAA+ chaperone p972013

    • Author(s)
      K. Noi, D. Yamamoto, S. Nishikori, K. Arita-Morioka, T. Ando, T. Ogura
    • Journal Title

      Structure

      Volume: 21 Issue: 11 Pages: 1992-2002

    • DOI

      10.1016/j.str.2013.08.017

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] CDC-48/p97 is required for proper meiotic chromosome segregation via controlling AIR-2/Aurora B kinase localization in Caenorhabditis elegans.2012

    • Author(s)
      Sasagawa Y, Higashitani A, Urano T, Ogura T, Yamanaka K.
    • Journal Title

      J Struct Biol.

      Volume: 179 Issue: 2 Pages: 104-111

    • DOI

      10.1016/j.jsb.2012.06.009

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Caenorhabditis elegans fidgetin homolog FIGL-1, a nuclear-localized AAA ATPase, binds to SUMO.2012

    • Author(s)
      Onitake, A., Yamanaka, K., Esaki, M., and Ogura, T.
    • Journal Title

      J. Struct. Biol.

      Volume: (in press) Issue: 2 Pages: 143-151

    • DOI

      10.1016/j.jsb.2012.04.022

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The C-terminal -helix of SPAS-1, a Caenorhabditis elegans spastin homologue, is crucial for microtubule severing.2012

    • Author(s)
      Onitake, A., Matsushita-Ishiodori, Y., Johjima, A., Esaki, M., Ogura, T., and Yamanaka, K.
    • Journal Title

      J. Struct. Biol.

      Volume: (in press) Issue: 2 Pages: 138-142

    • DOI

      10.1016/j.jsb.2012.04.010

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cdc48p/p97-mediated regulation of mitochondrial morphology is Vms1p independent.2012

    • Author(s)
      Esaki, M., and Ogura, T.
    • Journal Title

      J. Struct. Biol.

      Volume: (in press) Issue: 2 Pages: 112-120

    • DOI

      10.1016/j.jsb.2012.04.017

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Adaptors of p97 and disease-associated p97 mutations.2014

    • Author(s)
      Yamanaka, K., Murayama, Y., and Ogura, T.
    • Organizer
      231st IMEG seminars & Minisymposium
    • Place of Presentation
      熊本市 熊本大学発生医学研究所
    • Related Report
      2013 Annual Research Report
  • [Presentation] High-speed AFM observation of ATP-dependent rotation of the AAA chaperone p97 and its interaction with TDP-43 amyloid fibrils.2014

    • Author(s)
      Noi, K., Yamamoto, D., Arita-Morioka, K., Ando, T., and Ogura, T.
    • Organizer
      231st IMEG seminars & Minisymposium
    • Place of Presentation
      熊本市 熊本大学発生医学研究所
    • Related Report
      2013 Annual Research Report
  • [Presentation] Dynamics of p97 and the 26S proteasome in action revealed by high-speed atomic force microscopy2013

    • Author(s)
      Ogura, T., Noi, K., Okuno, T., Arita-Morioka, K., Yamamoto, D., Okawa, A., Tsuchiya, H., Saeki, Y., Ando, T., Esaki, M., and Yamanaka, K.
    • Organizer
      EMBO Workshop on AAA+ Proteins : from mechanism and disease to targets
    • Place of Presentation
      Neuss, Germany
    • Related Report
      2013 Final Research Report
  • [Presentation] Functional analysis of disease-associated mutant CDC-48/p97/VCP in C. elegans2013

    • Author(s)
      Yamanaka, K., Murayama, Y., and Ogura, T.
    • Organizer
      EMBO Workshop on AAA+ Proteins : from mechanism and disease to targets
    • Place of Presentation
      Neuss, Germany
    • Related Report
      2013 Final Research Report
  • [Presentation] Biochemical analysis of molecular mechanisms of the interaction between VCP/p97 and amyloid fibrils of TDP-432013

    • Author(s)
      Noi, K., Arita-Morioka, K., Ogi, H., Hirao, M., and Ogura, T.
    • Organizer
      EMBO Workshop on AAA+ Proteins : from mechanism and disease to targets
    • Place of Presentation
      Neuss, Germany
    • Related Report
      2013 Final Research Report
  • [Presentation] 分子シャペロンVCP/p97とTDP-43アミロイド線維の相互作用の分子機構の解析2013

    • Author(s)
      野井健太郎,有田-森岡健一,小椋光
    • Organizer
      第13回日本蛋白質科学会年会
    • Place of Presentation
      鳥取市、とりぎん文化会館
    • Related Report
      2013 Final Research Report
  • [Presentation] AAA chaperones, focusing on the molecular mechanism of p972013

    • Author(s)
      Ogura, T., Noi, K., Arita-Morioka, K., Yamamoto, D., Ando, T., Nishikori, S., Esaki, M., and Yamanaka, K.
    • Organizer
      EMBO Conference The biology of molecular chaperones : From molecules, organelles and cells to misfolding diseases
    • Place of Presentation
      Santa Margherita de Pula, Italy
    • Related Report
      2013 Final Research Report
  • [Presentation] Dynamics of p97 and the 26S proteasome in action revealed by high-speed atomic force microscopy.2013

    • Author(s)
      Ogura, T., Noi, K., Okuno, T., Arita-Morioka, K., Yamamoto, D., Okawa, A., Tsuchiya, H., Saeki, Y., Ando, T., Esaki, M., and Yamanaka, K.
    • Organizer
      EMBO Workshop on AAA+ Proteins
    • Place of Presentation
      Commundo Hotel, Neuss, Germany.
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Functional analysis of disease-associated mutant CDC-48/p97/VCP in C. elegans.2013

    • Author(s)
      Yamanaka, K., Murayama, Y., and Ogura, T.
    • Organizer
      EMBO Workshop on AAA+ Proteins
    • Place of Presentation
      Commundo Hotel, Neuss, Germany.
    • Related Report
      2013 Annual Research Report
  • [Presentation] Biochemical analysis of molecular mechanisms of the interaction between VCP/p97 and amyloid fibrils of TDP-43.2013

    • Author(s)
      Noi, K., Arita-Morioka, K., Ogi, H., Hirao, M., and Ogura, T.
    • Organizer
      EMBO Workshop on AAA+ Proteins
    • Place of Presentation
      Commundo Hotel, Neuss, Germany.
    • Related Report
      2013 Annual Research Report
  • [Presentation] AAA chaperones, focusing on the molecular mecanism of p97.2013

    • Author(s)
      Ogura, T., Noi, K., Arita-Morioka, K., Yamamoto, D., Ando, T., Nishikori, S., Esaki, M., and Yamanaka, K.
    • Organizer
      EMBO Conference
    • Place of Presentation
      Santa Margherita de Pula, Italy
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 線虫を用いた疾患型変異CDC-48/p97/VCPの機能解析.2013

    • Author(s)
      山中 邦俊, 村山 佑樹, 小椋 光
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸市、神戸国際展示場
    • Related Report
      2013 Annual Research Report
  • [Presentation] 分子シャペロンVCP/p97とTDP-43アミロイド線維の相互作用の分子機構の解析.2013

    • Author(s)
      野井 健太郎, 有田ー森岡 健一, 小椋 光
    • Organizer
      第13回日本蛋白質科学会年会
    • Place of Presentation
      鳥取市、とりぎん文化会館
    • Related Report
      2013 Annual Research Report
  • [Presentation] 分子シャペロンVCP/p97とTDP-43アミロイド線維の相互作用の分子機構の解析2012

    • Author(s)
      野井健太郎,有田-森岡健一,小椋光
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡,マリンメッセ福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] High-speed atomic force microscopy of ATP-dependent rotational movements of p97/VCP and its interaction with amyloid fibrils of TDP-432012

    • Author(s)
      Noi, K., Yamamoto, D., Arita-Morioka, K., Nishikori, S., Ando, T., and Ogura, T.
    • Organizer
      3rd Kanazawa Bio-AFM Workshop
    • Place of Presentation
      金沢、KKR Hotel Kanazawa
    • Related Report
      2013 Final Research Report
  • [Presentation] High-speed atomic force microscopy of ATP-dependent rotational movements of p97/VCP and its interaction with amyloid fibrils of TDP-43.2012

    • Author(s)
      Noi, K., Yamamoto, D., Arita-Morioka, K., Nishikori, S., Ando, T., and Ogura, T.
    • Organizer
      3rd Kanazawa Bio-AFM Workshop
    • Place of Presentation
      金沢・KKRホテル金沢
    • Related Report
      2012 Research-status Report
  • [Presentation] 分子シャペロンVCP/p97とTDP-43アミロイド線維の相互作用の分子機構の解析.2012

    • Author(s)
      野井 健太郎, 有田-森岡 健一, 小椋 光
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡・福岡国際会議場、マリンメッセ福岡
    • Related Report
      2012 Research-status Report
  • [Book] FtsH protease-mediated regulation of various cellular functions. Subcell. Biochem, 66, Regulated proteolysis in microorganisms. D. A. Dougan (ed.)2013

    • Author(s)
      Okuno, T., and Ogura, T.
    • Total Pages
      17
    • Publisher
      Springer
    • Related Report
      2012 Research-status Report
  • [Book] FtsH protease. In Handbook of Proteolytic Enzymes, 3rd edition, N. Rawlings and G. Salvesen (ed.)2013

    • Author(s)
      Ogura, T., Okuno, T., Suno, R., and Akiyama, Y.
    • Total Pages
      8
    • Publisher
      Elsevier Ltd.
    • Related Report
      2012 Research-status Report
  • [Remarks] 熊本大学発生医学研究所分子細胞制御分野のホームページ

    • URL

      http://mukb.medic.kumamoto-u.ac.jp/fukusei/index.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 熊本大学発生医学研究所分子細胞制御分野AAAホームページ

    • URL

      http://mukb.medic.kumamoto-u.ac.jp/AAA/aaainfo.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 熊本大学発生医学研究所のホームページ

    • URL

      http://www.imeg.kumamoto-u.ac.jp/index.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 熊本大学発生医学研究所分子細胞制御分野のホームページ

    • URL

      http://mukb.medic.kumamoto-u.ac.jp/fukusei/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 熊本大学発生医学研究所分子細胞制御分野 AAAホームページ

    • URL

      http://mukb.medic.kumamoto-u.ac.jp/AAA/aaainfo.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 熊本大学発生医学研究所のホームページ

    • URL

      http://www.imeg.kumamoto-u.ac.jp/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 熊本大学発生医学研究所分子細胞制御分野のホームページ

    • URL

      http://mukb.medic.kumamoto-u.ac.jp/fukusei/index.html

    • Related Report
      2012 Research-status Report
  • [Remarks] 熊本大学発生医学研究所分子細胞制御分野 AAAホームページ

    • URL

      http://mukb.medic.kumamoto-u.ac.jp/AAA/aaainfo.html

    • Related Report
      2012 Research-status Report
  • [Remarks] 熊本大学発生医学研究所のホームページ

    • URL

      http://www.imeg.kumamoto-u.ac.jp/index.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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