• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Analysis of neuronal cell death by ALS-associated misfolded protein aggregation with modulation of cellular RNA homeostasis

Research Project

Project/Area Number 23770215
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cell biology
Research InstitutionHokkaido University

Principal Investigator

KITAMURA Akira  北海道大学, 先端生命科学研究科(研究院), 助教 (10580152)

Project Period (FY) 2011 – 2014
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsALS / タンパク質凝集体 / 神経変性疾患 / 細胞内封入体 / RNA / TDP43 / 蛍光相関分光法 / RNA結合タンパク質 / 神経細胞死 / 蛍光分光イメージング / タンパク質品質管理
Outline of Final Research Achievements

TAR-RNA/DNA binding protein 43 kDa is a disease gene product associated with amyotrophic lateral sclerosis (ALS), a motor neuron disease. In this research, fluorescence correlation spectroscopy (FCS) measurement in cell lysate revealed that a 25 kDa carboxyl-terminal fragment of TDP43 (TDP25) formed aggregation after dissociation of RNA. Next, TDP43 was sequestrated into cytoplasmic inclusion bodies of TDP25 in living cells. Neuronal cells expressing TDP25 showed higher cell death efficiency than that of TDP43. These results suggest that TDP25 may be an aggregation-causative and toxic seed, and RNA may play an important role for inhibition of aggregation-formation of TDP25.

Report

(4 results)
  • 2014 Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (17 results)

All 2014 2013 2012 2011 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 2 results) Presentation (8 results)

  • [Journal Article] Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ AT Pase, which dynamically changes its oligomeric state2014

    • Author(s)
      Daisuke Morito, Kouki Nishikawa, Jun Houseki, Akira Kitamura, Yuri Kotani, Kazumi Kiso, Masataka Kinjo, Yoshimori Fujiyoshi & Kazuhiro Nagata
    • Journal Title

      SCIENTIFIC REPORTS

      Volume: Vol. 4 Issue: 1 Pages: 4442-4442

    • DOI

      10.1038/srep04442

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysregulation of the Proteasome Enhances the Toxicity of ALS-linked Mutant SOD12014

    • Author(s)
      Kitamura, A., Inada, N., Kubota, H., Matsumoto, G., Kinjo, M., Morimoto, R.I., Nagata, K
    • Journal Title

      Genes to Cells

      Volume: 3 Issue: 3 Pages: 209-224

    • DOI

      10.1111/gtc.12125

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prefoldin prevents aggregation of alpha-synuclein.2014

    • Author(s)
      Takano M., Tashiro E., Kitamura A., Maita H., Iguchi-Ariga M.M.S., Kinjo M., Ariga H.
    • Journal Title

      Brain Research

      Volume: 1542 Pages: 186-194

    • DOI

      10.1016/j.brainres.2013.10.034

    • NAID

      120005397867

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The interaction of Hsp104 with yeast prion Sup35 as analyzed by fluorescence cross-correlation spectroscopy.oligomeric state.2013

    • Author(s)
      Ohta S., Kawai-Noma S., Kitamura A., Pack C.G., Kinjo M., Taguchi H.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 442 Issue: 1-2 Pages: 28-32

    • DOI

      10.1016/j.bbrc.2013.10.147

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prefoldin protects neuronal cells from polyglutamine toxicity by preventing aggregation formation.2013

    • Author(s)
      Tashiro E, Zako T, Muto H, Itoo Y, Sorgjerd K, Terada N, Abe A, Miyazawa M, Kitamura A, Kitaura H, Kubota H, Maeda M, Momoi T, Iguchi-Ariga SM, Kinjo M, Ariga H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 288 Issue: 27 Pages: 19958-19972

    • DOI

      10.1074/jbc.m113.477984

    • NAID

      120005323603

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nonmuscle myosin II folds into a 10S form via two portions of tail for dynamic subcellular loacalization.2013

    • Author(s)
      Kiboku T.
    • Journal Title

      Genes to Cells.

      Volume: 18(2) Issue: 2 Pages: 90-109

    • DOI

      10.1111/gtc.12021

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Direct association of unfolded proteins with mammalian ER stress sensor, IRE1 beta.2012

    • Author(s)
      Oikawa D.
    • Journal Title

      PLoS One.

      Volume: 7(12) Issue: 12 Pages: e51290-e51290

    • DOI

      10.1371/journal.pone.0051290

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Atg9 vesicles are an important membrane source during early steps of autophagosome formation.2012

    • Author(s)
      Yamamoto H.
    • Journal Title

      J. Cell Biol.

      Volume: 198(2) Issue: 2 Pages: 219-233

    • DOI

      10.1083/jcb.201202061

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Analyzing the aggregation of polyglutamine-expansion proteins and its modulation by molecular chaperones.2011

    • Author(s)
      Kubota H, Kitamura A, Nagata K.
    • Journal Title

      Methods

      Volume: 53 Pages: 267-274

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Characterization of cytoplasmic and nuclear inclusion of ALS-causative TDP43 protein2011

    • Author(s)
      Akira Kitamura, Yusaku Nakayama, Masataka Kinjo
    • Organizer
      第63回 日本細胞生物学会大会
    • Place of Presentation
      北海道大学(札幌市)
    • Related Report
      2011 Research-status Report
  • [Presentation] Aggregation and disaggregation of aggregate-prone proteins: Which is toxic?2011

    • Author(s)
      Akira Kitamura
    • Organizer
      奈良先端大シンポジウム(招待講演)
    • Place of Presentation
      奈良先端大学院大学(奈良県)
    • Related Report
      2011 Research-status Report
  • [Presentation] RNA inhibits the toxicity of carboxyl-terminal fragments of ALS-causative TDP43 protein2011

    • Author(s)
      Akira Kitamura, Yusaku Nakayama, Masataka Kinjo
    • Organizer
      Cold Spring Harbor Asia, "Protein Homeostasis in Health & Disease"
    • Place of Presentation
      Cold Spring Harbor Asia (中国)
    • Related Report
      2011 Research-status Report
  • [Presentation] Characterization of cytoplasmic and nuclear inclusion of ALS-causative TDP43 protein2011

    • Author(s)
      Akira Kitamura, Yusaku Nakayama, Masataka Kinjo
    • Organizer
      特定領域「タンパク質の社会」若手シンポジウム
    • Place of Presentation
      アクティプラザ琵琶(滋賀県)
    • Related Report
      2011 Research-status Report
  • [Presentation] プロテアソーム活性阻害からの回復過程における 細胞毒性発現機構の解明

    • Author(s)
      北村朗,永田和宏,金城政孝
    • Organizer
      2013年度若手イメージング研究会
    • Place of Presentation
      東京理科大学野田キャンパス(千葉県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] プロテアソーム活性阻害からの回復過程における 細胞毒性発現機構の解明

    • Author(s)
      北村朗,永田和宏,金城政孝
    • Organizer
      第36回 日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(神戸市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Increased toxicity and aggregate formation of carboxyl-terminal fragments of ALS-linked TDP43 protein in cytoplasm.

    • Author(s)
      Kitamura A., Nakayama Y. Shibasaki A., & Kinjo M.
    • Organizer
      FASEB summer research conference
    • Place of Presentation
      Vermont Academy (USA)
    • Related Report
      2012 Research-status Report
  • [Presentation] ALS関連TDP43タンパク質のカルボキシル末端断片の細胞質における凝集体形成と毒性はRNAによって防御されている

    • Author(s)
      北村朗,柴崎愛,中山祐作,金城政孝
    • Organizer
      第35回 日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Related Report
      2012 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi