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Establishment of a system for monitoring endoplasmic reticulum redox state in mammalian cells

Research Project

Project/Area Number 24659429
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionNagoya University

Principal Investigator

ISHIGAKI Shinsuke  名古屋大学, 医学(系)研究科(研究院), 助教 (40378170)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsER stress / 神経変性疾患 / ALS / 小胞体ストレス
Research Abstract

The endoplasmic reticulum (ER) performs a critical role in the oxidative folding of nascent proteins such that perturbations to ER homeostasis may lead to protein misfolding and subsequent pathological processes. Among the mechanisms for maintaining ER homeostasis is a redox regulation, which is a critical determinant of the fate of ER stressed cells. Here we report the establishment of a system for monitoring ER redox state in mammalian cells. The new ER redox sensing system was developed based on the previously described monitoring system in yeast. Our system could successfully monitor the dynamic ER redox state in mammalian cells. Using this system, we find that manipulation of ER oxidases changes ER redox state. The mammalian ER redox sensing system could be used to study the mechanisms of ER redox regulation and provide a foundation for an approach to develop novel therapeutic modalities for human diseases related to dysregulated ER homeostasis including neurodegeneration.

Report

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

    (17 results)

All 2014 2013 2012 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (11 results) (of which Invited: 1 results)

  • [Journal Article] Lower motor neuron involvement in TAR DNA-binding protein of 43 kDa-related frontotemporal lobar degeneration and amyotrophic lateral sclerosis.2014

    • Author(s)
      Riku Y, Watanabe H, Yoshida M, Tatsumi S, Mimuro M, Iwasaki Y, Katsuno M, Iguchi Y, Masuda M, Senda J, Ishigaki S, Udagawa T, Sobue G
    • Journal Title

      JAMA Neurol.

      Volume: 71 Issue: 2 Pages: 172-179

    • DOI

      10.1001/jamaneurol.2013.5489

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The ALS/FTLD-related RNA-binding proteins TDP-43 and FUS have common downstream RNA targets in cortical neurons2013

    • Author(s)
      Honda D, Ishigaki S, Iguchi Y, Fujioka Y, Udagawa T, Masuda A, Ohno K, Katsuno M, Sobue G.
    • Journal Title

      FEBS Open Bio.

      Volume: 20 Issue: 1 Pages: 1-10

    • DOI

      10.1016/j.fob.2013.11.001

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of a system for monitoring endoplasmic reticulum redox state in mammalian cells.2013

    • Author(s)
      Kanekura K, Ishigaki S, Merksamer P, Papa F, Urano F.
    • Journal Title

      Lab Invest.

      Volume: 93 Issue: 11 Pages: 1254-8

    • DOI

      10.1038/labinvest.2013.112

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] FUS-regulated region- and cell-type-specific transcriptome is associated with cell selectivity in ALS/FTLD.2013

    • Author(s)
      Fujioka Y, Ishigaki S, Masuda A, Iguchi Y, Udagawa T, Watanabe H, Katsuno M, Ohno K, Sobue G.
    • Journal Title

      Sci Rep.

      Volume: 3 Issue: 1 Pages: 2388-2388

    • DOI

      10.1038/srep02388

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Thioredoxin-interacting protein mediates ER stress-inducedβcell death through initiation of the inflammasome2012

    • Author(s)
      Oslowski CM, Hara T, O'Sullivan-Murphy B, Kanekura K, Lu S, Hara M, Ishigaki S, Zhu LJ, Hayashi E, Hui ST, Greiner D, Kaufman RJ, Bortell R, Urano F.
    • Journal Title

      Cell Metab

      Volume: 16(2) Issue: 2 Pages: 265-73

    • DOI

      10.1016/j.cmet.2012.07.005

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Position-dependent FUS-RNA interactions regulate alternative splicing events and transcriptions.2012

    • Author(s)
      Ishigaki S, Masuda A, Fujioka Y, Iguchi Y, Katsuno M, Shibata A, Urano F, Sobue G, Ohno K
    • Journal Title

      Sci Rep

      Volume: 2 Issue: 1 Pages: 529-529

    • DOI

      10.1038/srep00529

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] FUS regulates alternative splicing patterns of Mapt by cooperating with PSF/SFPQ : a novel link between FUS and Tau in the pathogenesis of ALS and FTLD. RNA Metabolism in Neurological Disease2013

    • Author(s)
      Shinsuke Ishigaki, Yusuke Fujioka, Tsuyoshi Udagawa, Daiyu Honda, Masahisa Katsuno, and Gen Sobue
    • Organizer
      8th Brain Research Conference
    • Place of Presentation
      San Diego, CAアメリカ合衆国
    • Year and Date
      2013-11-17
    • Related Report
      2013 Final Research Report
  • [Presentation] FUS regulates alternative splicing patterns of Mapt by cooperating with PSF/SFPQ in association with clinicopathological features of ALS/FTLD : a novel link between FUS and Tau in the pathogenesis of ALS and FTLD2013

    • Author(s)
      Shinsuke Ishigaki, Yusuke Fujioka, Tsuyoshi Udagawa, Daiyu Honda, Masahisa Katsuno, and Gen Sobue
    • Organizer
      The 43rd Society for Neuroscience annual meeting
    • Place of Presentation
      San Diego, CAアメリカ合衆国
    • Year and Date
      2013-11-10
    • Related Report
      2013 Final Research Report
  • [Presentation] FUS regulates alternative splicing patterns of Mapt by cooperating with PSF/SFPQ in association with clinicopathological features of ALS/FTLD: a novel link between FUS and Tau in the pathogenesis of ALS and FTLD.2013

    • Author(s)
      Shinsuke Ishigaki, Yusuke Fujioka, Tsuyoshi Udagawa, Daiyu Honda, Masahisa Katsuno, and Gen Sobue
    • Organizer
      The 43rd Society for Neuroscience annual meeting
    • Place of Presentation
      San Diego, CA アメリカ合衆国
    • Related Report
      2013 Annual Research Report
  • [Presentation] Comparison of Fus-regulating gene expression and alternative splicing profiles among different cell lineages in the central nervous system2012

    • Author(s)
      Shinsuke Ishigaki, Yusuke Fujioka, Akio Masuda, Yohei Iguchi, Masahisa Katsuno, Kinji Ohno, and Gen Sobue
    • Organizer
      The 42nd Society for Neuroscience annual meeting
    • Place of Presentation
      New Orleans, LAアメリカ合衆国
    • Year and Date
      2012-10-14
    • Related Report
      2013 Final Research Report
  • [Presentation] Comparison of Fus-regulating gene expression and alternative splicing profiles among different cell lineages in the central nervous system.2012

    • Author(s)
      Shinsuke Ishigaki, Yusuke Fujioka, Akio Masuda, Yohei Iguchi, Masahisa Katsuno, Kinji Ohno, and Gen Sobue
    • Organizer
      The 42nd Society for Neuroscience annual meeting
    • Place of Presentation
      New Orleans, LA
    • Related Report
      2012 Research-status Report
  • [Presentation] FUS regulates alternative splicing patterns of Mapt by cooperating with PSF/SFPQ in neurons: a novel link between FUS and Tau in the pathogenesis of ALS and FTLD.2012

    • Author(s)
      Shinsuke Ishigaki, Yusuke Fujioka, and Gen Sobue
    • Organizer
      6th International Symposium of Nanomedicine
    • Place of Presentation
      Matsue, Japan
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] ALSにおけるFUS/TLSの質的機能喪失と病態:FUS/TLSの核内高分子複合体の機能解析から2012

    • Author(s)
      石垣 診祐、 藤岡 祐介、 田中 章景、 祖父江 元
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 家族性ALS原因遺伝子FUS/TLSノックダウンに伴う選択的splicing変化2012

    • Author(s)
      藤岡 祐介、石垣 診祐、増田 章男、大野 欽司、祖父江 元
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] FUS regulates alternative splicing patterns of Mapt by cooperating with PSF/SFPQ: a novel link between FUS and Tau in the pathogenesis of ALS and FTLD.2012

    • Author(s)
      Shinsuke Ishigaki, Yusuke Fujioka, Yohei Okada, Akio Masuda, Kinji Ohno, and Gen Sobue
    • Organizer
      The 35th annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] Comparison of Fus-regulating gene expression and alternative splicing profiles among different primary cells in central nervous system.2012

    • Author(s)
      Yusuke Fujioka, Shinsuke Ishigaki, Akio Masuda, Kinji Ohno, and Gen Sobue
    • Organizer
      The 35th annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] FUS regulates alternative splicing patterns of Mapt by cooperating with PSF/SFPQ: a novel link between FUS and Tau in the pathogenesis of ALS and FTLD.

    • Author(s)
      Shinsuke Ishigaki, Yusuke Fujioka, Tsuyoshi Udagawa, Daiyu Honda, Masahisa Katsuno, and Gen Sobue
    • Organizer
      RNA Metabolism in Neurological Disease, 8th Brain Research Conference
    • Place of Presentation
      San Diego, CA アメリカ合衆国
    • Related Report
      2013 Annual Research Report

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

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