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Genetic analysis of the systemic damage response via caspase pathway to maintain homeostasis

Planned Research

Project AreaHomeostatic inflammation: Molecular basis and dysregulation
Project/Area Number 21117006
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe Institute of Physical and Chemical Research (2011-2013)
The University of Tokyo (2009-2010)

Principal Investigator

KURANAGA Erina  独立行政法人理化学研究所, 発生・再生科学総合研究センター, チームリーダー (90376591)

Project Period (FY) 2009-07-23 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥68,770,000 (Direct Cost: ¥52,900,000、Indirect Cost: ¥15,870,000)
Fiscal Year 2013: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2012: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Fiscal Year 2011: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
Fiscal Year 2010: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Fiscal Year 2009: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Keywordsカスパーゼ / 非感染性炎症 / ショウジョウバエ / 内因性リガンド / 炎症 / 病原体センサー / 細胞死 / 自然炎症
Research Abstract

In this study, we focused on stress responses and metabolic alterations in the Drosophila apaf-1 (dpf-1) mutant, in which caspase activation and subsequent apoptosis are severely impaired. The dpf-1 mutant was found to be sensitive to injury- and starvation-stress. We show that dpf-1 mutant has defects in homeostatic gut cell renewal and that inhibiting caspase activity in fly enterocytes results in the production of systemic lethal factors after wounding. We then conducted metabolomic analyses of the hemolymph in dpf-1 mutants to investigate the physiological consequences of caspase inhibition. Several metabolites were found at higher levels in dpf-1 mutants than in wild type, which for at least one of the metabolites, was likely due to alteration of expression levels of putative metabolic enzymes in the fat body. Together, these results suggest caspase activity is required in the gut to regulate the systemic defense response in order to overcome stress in vivo.

Report

(6 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (56 results)

All 2014 2013 2012 2011 2010 2009 Other

All Journal Article (28 results) (of which Peer Reviewed: 24 results,  Open Access: 1 results) Presentation (26 results) (of which Invited: 5 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis2014

    • Author(s)
      Obata F, Kuranaga E, Tomioka K, Ming M, Takeishi A, Chen CH, Soga T, Miura M
    • Journal Title

      Cell Rep.

      Volume: 7 Issue: 3 Pages: 821-833

    • DOI

      10.1016/j.celrep.2014.03.046

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Persephone/Spatzle pathogen sensors mediate the activation of Toll receptor signaling in response to endogenous danger signals in apoptosis-deficient Drosophila2014

    • Author(s)
      Ming M, Obata F, Kuranaga E, Miura M
    • Journal Title

      J Biol Chem.

      Volume: 289 Issue: 11 Pages: 7558-7568

    • DOI

      10.1074/jbc.m113.543884

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo monitoring of caspase activation using a fluorescence resonance energy transfer-based fluorescent probe.2014

    • Author(s)
      Yamaguchi, Y., Kuranaga, E., Nakajima, Y., Koto, A., Takemoto, K., and Miura, M.
    • Journal Title

      Methods Enzymol.

      Volume: in press

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Homeostatic epithelial renewal in the gut is required for dampening a fatal systemic wound response in Drosophila2013

    • Author(s)
      Takeishi A, Kuranaga E, Tonoki A, Misaki K, Yonemura S, Kanuka H, Miura M
    • Journal Title

      Cell Rep.

      Volume: 3 Issue: 3 Pages: 919-930

    • DOI

      10.1016/j.celrep.2013.02.022

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RNA binding mediates neurotoxicity in the transgenic Drosophila model of TDP-43 proteinopathy.2013

    • Author(s)
      Ihara R, Matsukawa K, Nagata Y, Kunugi H, Tsuji S, Chihara T, Kuranaga E, Miura M, Wakabayashi T, Hashimoto T, Iwatsubo T.
    • Journal Title

      Hum Mol Genet.

      Volume: 22(22) Issue: 22 Pages: 4474-4484

    • DOI

      10.1093/hmg/ddt296

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞死が推進する上皮組織の維持・形成と移動―死してその先にあるもの2013

    • Author(s)
      倉永 英里奈
    • Journal Title

      医学のあゆみ

      Volume: 246 (5) Pages: 385-391

    • Related Report
      2013 Annual Research Report
  • [Journal Article] The kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP52012

    • Author(s)
      Yusuke Sekine, Ryo Hatanaka, Takeshi Watanabe. Naoki Sono, Shun-ichiro Iemura, Tohru Natsume, Erina Kuranaga, Masayuki Miura, Kohsuke Takeda, and Hidenori Ichijo
    • Journal Title

      Molecular Cell

      Volume: 48 Issue: 5 Pages: 1-13

    • DOI

      10.1016/j.molcel.2012.09.018

    • NAID

      120007150217

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Beyond apoptosis : caspase regulatory mechanisms and functions in vivo2012

    • Author(s)
      Kuranaga E
    • Journal Title

      Genes Cells.

      Volume: 17 Issue: 2 Pages: 83-97

    • DOI

      10.1111/j.1365-2443.2011.01579.x

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Beyond apoptosis : caspase regulatory mechanisms and functions in vivo2012

    • Author(s)
      Erina Kuranaga
    • Journal Title

      Genes Cells

      Volume: 17(2) Pages: 83-97

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Non-autonomusapoptosis is triggered by local cell cycl eprogression during epithelial replacement in Drosophila2011

    • Author(s)
      Nakajima, Y-I, Kuranaga, E., Sugimura, K., Miyawaki, A., and Miura, M.
    • Journal Title

      Mol. Cell Biol

      Volume: 31 Issue: 12 Pages: 2499-2512

    • DOI

      10.1128/mcb.01046-10

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aging causes distinct characteristics of polyglutamine amyloids in vivo2011

    • Author(s)
      Tonoki, A., E. Kuranaga, N. Ito, Y. Nekooki-Machida, Tanaka, M., and Miura, M.
    • Journal Title

      Genes to Cells

      Volume: 16 Issue: 5 Pages: 557-564

    • DOI

      10.1111/j.1365-2443.2011.01505.x

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Apoptosis controls the speed of looping morphogenesis in Drosophila male terminalia2011

    • Author(s)
      Kuranaga, E., Matsunuma, T., Kanuka, H., Takemoto, K., Koto, A., Kimura, K and Miura, M.
    • Journal Title

      Development

      Volume: 138 Issue: 8 Pages: 1493-1499

    • DOI

      10.1242/dev.058958

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Apoptosis ensures spacing pattern formation of Drosophila sensory organs2011

    • Author(s)
      Koto, A., Kuranaga, E., and Miura, M.
    • Journal Title

      Current Biol

      Volume: 21 Issue: 4 Pages: 278-287

    • DOI

      10.1016/j.cub.2011.01.015

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Caspase signaling in animal development2011

    • Author(s)
      Kuranaga E
    • Journal Title

      Dev Growth Differ.

      Volume: 53 Issue: 2 Pages: 137-48

    • DOI

      10.1111/j.1440-169x.2010.01237.x

    • NAID

      10027899646

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] ショウジョウバエにおける炎症応答と組織再生2011

    • Author(s)
      小幡史明、倉永英里奈、三浦正幸
    • Journal Title

      生体の科学

      Volume: 62 Pages: 249-256

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Journal Article] p38 MAPKs regulate the expression of genes in the dopamine synthesis pathway through phosphorylation of NR4A nuclear receptors2011

    • Author(s)
      Sekine Y, Takagahara S, Hatanaka R, Watanabe T, Oguchi H, Noguchi T, Naguro I, Kobayashi K, Tsunoda M, Funatsu T, Nomura H, Toyoda T, Matsuki N, Kuranaga E, Miura M, Takeda K, Ichijo H
    • Journal Title

      J Cell Sci

      Volume: 124 Pages: 3006-16

    • NAID

      120007150216

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] β-Galactosidase fluorescence probe with improved cellular accumulation based on a spirocyclized rhodol scaffold2011

    • Author(s)
      Kamiya M, Asanuma D, Kuranaga E, Takeishi A, Sakabe M, Miura M, Nagano T, Urano Y
    • Journal Title

      J Am Chem Soc

      Volume: 133(33) Pages: 12960-3

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aging causes distinct characteristics of polyglutamine amyloids in vivo2011

    • Author(s)
      Tonoki A, Kuranaga E, Ito N, Nekooki-Machida Y, Tanaka M, Miura M
    • Journal Title

      Genes Cells

      Volume: 16(5) Pages: 557-64

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Apoptosis ensures spacing pattern formation of Drosophila sensory organs2011

    • Author(s)
      Koto A, Kuranaga E, Miura M
    • Journal Title

      Curr Biol

      Volume: 21(4) Pages: 278-87

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Caspase signaling in animal development2011

    • Author(s)
      Kuranaga E.
    • Journal Title

      Dev Growth Differ

      Volume: 53(2) Pages: 137-48

    • NAID

      10027899646

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nonautonomous apoptosis is triggered by local cell cycle progression during epithelial replacement in Drosophila2011

    • Author(s)
      Nakajima Y, Kuranaga E, Sugimura K, Miyawaki A, Miura M
    • Journal Title

      Mol Cell Biol

      Volume: 31(12) Pages: 2499-512

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Caspase signaling in animal development.2011

    • Author(s)
      Kuranaga E.
    • Journal Title

      Dev Growth Differ.

      Volume: 53(2) Pages: 137-48

    • NAID

      10027899646

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Apoptosis ensures spacing pattern formation of Drosophila sensory organs.2011

    • Author(s)
      Koto A, Kuranaga E, Miura M.
    • Journal Title

      Curr Biol.

      Volume: 21(4) Pages: 278-87

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ショウジョウバエにおける組織傷害応答2010

    • Author(s)
      小幡史明、倉永英里奈、三浦正幸
    • Journal Title

      炎症と免疫

      Volume: 18 Pages: 222-227

    • Related Report
      2013 Final Research Report 2010 Annual Research Report
  • [Journal Article] Temporal regulation of Drosophila IAP determines the dual functions of caspases in sensory organ development2009

    • Author(s)
      Koto, A., Kuranaga, E., and Miura, M
    • Journal Title

      J. Cell Biol

      Volume: 187 Issue: 2 Pages: 219-321

    • DOI

      10.1083/jcb.200905110

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetic evidence linking age-dependent attenuation of the 26S proteasome with the aging process2009

    • Author(s)
      Tonoki A, Kuranaga E, Tomioka T, Hamazaki J, Murata S, Tanaka K, Miura M
    • Journal Title

      Mol Cell Biol.

      Volume: 29 Issue: 4 Pages: 1095-106

    • DOI

      10.1128/mcb.01227-08

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Temporal regulation of Drosophila IAP1 determines caspase functions in sensory organ development.2009

    • Author(s)
      Koto A.
    • Journal Title

      J.Cell Biol.

      Volume: 187 Pages: 219-321

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic evidence linking age-dependent attenuation of the 26S proteasome with aging process.2009

    • Author(s)
      Tonoki A.
    • Journal Title

      Mol.Cell Biol.

      Volume: 29 Pages: 1095-1106

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 上皮細胞の集団移動を可能にする細胞平面の運動と力学モデル2014

    • Author(s)
      倉永 英里奈
    • Organizer
      細胞システムコロキウム
    • Place of Presentation
      和光市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 上皮細胞の集団移動を可能にする細胞平面の運動と力学的考察2014

    • Author(s)
      倉永 英里奈
    • Organizer
      東工大生命科学シンポジウム
    • Place of Presentation
      神奈川県、横浜市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Collective unidirectional motion of epithelial cells induced by planar cell dynamics during looping morphogenesis of Drosophila male terminalia2013

    • Author(s)
      Kuranaga E
    • Organizer
      Asia Pacific Drosophila Research Conference
    • Place of Presentation
      Korea
    • Related Report
      2013 Final Research Report
  • [Presentation] Collective unidirectional motion of epithelial cells induced by planar cell dynamics2013

    • Author(s)
      Kuranaga E
    • Organizer
      European Drosophila Research Conference
    • Place of Presentation
      Spein
    • Related Report
      2013 Final Research Report
  • [Presentation] Collective unidirectional motion of epithelial cells that supported by planar cell dynamics during Drosophila looping morphogenesis2013

    • Author(s)
      Erina Kuranaga
    • Organizer
      CDB-Balcerona joint meeting
    • Place of Presentation
      Balcerona, Spain
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Collective unidirectional motion of epithelial cells induced by planar cell dynamics during looping morphogenesis of Drosophila male terminalia2013

    • Author(s)
      Erina Kuranaga
    • Organizer
      Asia Pacific Drosophila Research Conference
    • Place of Presentation
      Seul, South Korea
    • Related Report
      2013 Annual Research Report
  • [Presentation] Collective unidirectional motion of epithelial cells supported by planar cell dynamics during Drosophila organogenesis: Experimental approach2013

    • Author(s)
      Erina Kuranaga
    • Organizer
      日本発生生物学会
    • Place of Presentation
      島根県、松江市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Collective unidirectional motion of epithelial cells induced by planar cell dynamics2013

    • Author(s)
      Erina Kuranaga
    • Organizer
      京大生命科学シンポジウム
    • Place of Presentation
      京都市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 上皮組織における集団的細胞移動を可能にする細胞平面の運動と作動原理2013

    • Author(s)
      倉永 英里奈
    • Organizer
      日本生化学会
    • Place of Presentation
      神奈川県、横浜市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Collective unidirectional motion of epithelial cells induced by planar cell dynamics2013

    • Author(s)
      Erina Kuranaga
    • Organizer
      EDRC
    • Place of Presentation
      Balcerona, Spain
    • Related Report
      2013 Annual Research Report
  • [Presentation] 回転する器官形成を支える上皮細胞集団移動のしくみ2013

    • Author(s)
      倉永 英里奈
    • Organizer
      発生生物学会秋季シンポジウム
    • Place of Presentation
      神戸市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Genetic analysis of the systemic damage response via caspase pathway to maintain homeostasis2012

    • Author(s)
      Kuranaga E
    • Organizer
      IEIIS2012 Joint with Homeostatic Inflammation Symposium
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Final Research Report 2012 Annual Research Report
  • [Presentation] Genetic approaches to identify risk factors for the onset of age-related neurodegenerative disorders2011

    • Author(s)
      Ayako Tonoki, Erina Kuranaga, Masayuki Miura
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜(招待講演)
    • Year and Date
      2011-12-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] ショウジョウバエカスパーゼ活性化因子 dapaf-1変異体における飢餓 /酸化ストレス応答異常とメタボローム解析2011

    • Author(s)
      小幡史明、倉永英里奈, 他
    • Place of Presentation
      横浜
    • Year and Date
      2011-09-21
    • Related Report
      2013 Final Research Report
  • [Presentation] ショウジョウバエカスパーゼ活性化因子dapaf-1変異体における飢餓/酸化ストレス応答異常とメタボローム解析2011

    • Author(s)
      小幡史明、倉永英里奈, 他
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2011-09-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] 晩発性発症を規定するリスクファクターの探索2011

    • Author(s)
      倉永英里奈
    • Organizer
      成人病の病因・病態の解明に関する研究助成第17回研究発表会
    • Place of Presentation
      大阪(招待講演)
    • Year and Date
      2011-07-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] 小さな生き物から学ぶーからだの形づくりと病気のしくみ2010

    • Author(s)
      倉永英里奈
    • Organizer
      BMB2010市民公開講座「広がる生命科学の世界-からだの形づくりから病気の克服までー」
    • Place of Presentation
      東京
    • Year and Date
      2010-12-11
    • Related Report
      2013 Final Research Report
  • [Presentation] Genetic analysis of homeostatic maintenance against stressed condition2010

    • Author(s)
      Kuranaga, E., Miura, M.
    • Organizer
      The Homeostatic Inflammation Symposium I "Deciphering a link between pathogen sensors and inflammatory diseases"
    • Place of Presentation
      Tokyo
    • Year and Date
      2010-07-28
    • Related Report
      2013 Final Research Report
  • [Presentation] Genetic analysis of homeostatic maintenance against stressed condition.2010

    • Author(s)
      Kuranaga E., Miura, M
    • Organizer
      The Homeostatic Inflammation Symposium I "Deciphering a link between pathogen sensors and inflammatory diseases"
    • Place of Presentation
      東京
    • Year and Date
      2010-07-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] ショウジョウバエ遺伝学を用いた医薬学研究2010

    • Author(s)
      倉永英里奈
    • Organizer
      第8回 Cardiovascular Metabolism and Aging Conference
    • Place of Presentation
      東京
    • Year and Date
      2010-07-02
    • Related Report
      2013 Final Research Report
  • [Presentation] ショウジョウバエ遺伝学を用いた医薬学研究2010

    • Author(s)
      倉永英里奈
    • Organizer
      第8回Cardiovascular Metabolism and Aging Conference
    • Place of Presentation
      東京
    • Year and Date
      2010-07-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Deciphering the physiological roles of caspase in vivo2010

    • Author(s)
      Kuranaga, E., Miura, M.
    • Organizer
      BMB2010
    • Place of Presentation
      Kobe
    • Related Report
      2013 Final Research Report
  • [Presentation] In vivo analysis of cell death during organogenesis2010

    • Author(s)
      Kuranaga, E., Miura, M.
    • Organizer
      APRU Research Symposium 2010
    • Place of Presentation
      Kyoto
    • Related Report
      2013 Final Research Report
  • [Presentation] カスパーゼの関与する生体防御機構-ショウジョウバエを用いたアプローチー2009

    • Author(s)
      倉永英里奈
    • Organizer
      第18回内毒素・LPS研究会
    • Place of Presentation
      東京
    • Year and Date
      2009-06-20
    • Related Report
      2013 Final Research Report 2009 Annual Research Report
  • [Presentation] In vivo analysis of apoptosis during reproductive organ development in Drosophila2009

    • Author(s)
      Kuranaga E.
    • Organizer
      International Joint Symposium on "Cell Fate Regulation Research: Molecular Basis and Therapeutic Potential"
    • Place of Presentation
      Kumamoto
    • Related Report
      2013 Final Research Report
  • [Presentation] ショウジョウバエを用いた新たなホメオスタシス維持機構の遺伝学的解明2009

    • Author(s)
      倉永英里奈
    • Organizer
      第82回日本生化学会大会シンポジウム
    • Place of Presentation
      神戸
    • Related Report
      2009 Annual Research Report
  • [Book] seriesモデル動物利用マニュアル生物機能モデルと新しいリソース・リサーチツール「ショウジョウバエを用いた生体イメージング」2011

    • Author(s)
      倉永英里奈, 他
    • Publisher
      株式会社エル・アイ・シー
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.cdb.riken.jp/jp/02_research/0202_creative27.html

    • Related Report
      2011 Annual Research Report

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Published: 2009-04-01   Modified: 2018-03-28  

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