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Transglutaminase-catalyzed protein-protein crosslinking maintains the innate immunity in Drosophila

Research Project

Project/Area Number 26860333
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionKyushu University

Principal Investigator

Shibata Toshio  九州大学, 高等研究院, 助教 (00614257)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords腸管免疫 / 囲食膜 / トランスグルタミナーゼ / ショウジョウバエ / 外毒素プロテアーゼ / 経口感染 / タンパク質架橋 / キイロショウジョウバエ / TGase / IMD経路 / 自然免疫 / 免疫寛容 / 架橋反応 / 活性酸素
Outline of Final Research Achievements

Intestinal homeostasis is ensured by a subtle balance between bacteria and host immunity. Gut epithelial barriers, such as the mucus layer in mammals and the peritrophic matrix in invertebrates, have a protective function for hosts, as they are impermeable to the invading intestinal microbes. In this study, we discovered, in the fly Drosophila melanogaster, that transglutaminase, known to be molecular glue involved in protein-protein covalent bond formation, is essential for peritrophic matrix formation to convert a peritrophic protein Drosocrystallin into a stable fiber-like structure and to inhibit the pathogenesis against pathogenic bacteria. Knockdown of transglutaminase gene, the permeability of the peritrophic matrix was increased and the fly exhibited highly susceptibility against a bacterial toxic protease. Transglutaminase contributes to form the stable mesh-like barrier on the peritrophic matrix and tolerant for pathogenic microorganisms.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (14 results)

All 2015 2014 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Invited: 2 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Crosslinking of a peritrophic matrix protein protects gut epithelia from bacterial exotoxins.2015

    • Author(s)
      Shibata, T., Maki, K., Hadano, J., Fujikawa, T., Kitazaki, K., Koshiba, T., and Kawabata, S.
    • Journal Title

      PLoS Pathogens

      Volume: 11 Issue: 10 Pages: 1-15

    • DOI

      10.1371/journal.ppat.1005244

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The N-terminal Arg residue is essential for autocatalytic activation of a lipopolysaccharide-responsive protease zymogen2014

    • Author(s)
      Kobayashi, Y., Shiga, T., Shibata, T., Sako, M., Maenaka, K., Koshiba, T., Mizumura, H., Oda, T., and Kawabata, S.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 289 Issue: 37 Pages: 25987-25995

    • DOI

      10.1074/jbc.m114.586933

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 脂質修飾が引き起こすショウジョウバエトランスグルタミナーゼの細胞内局在性の変化2015

    • Author(s)
      柴田俊生、羽田野仁喜、田川圭介、川畑俊一郎
    • Organizer
      BMB2015
    • Place of Presentation
      兵庫県
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 脂質修飾が引き起こす架橋酵素の細胞内局在性の変化2015

    • Author(s)
      柴田俊生、羽田野仁喜、田川圭介、川畑俊一郎
    • Organizer
      日本比較免疫学会
    • Place of Presentation
      福井県
    • Year and Date
      2015-08-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] ショウジョウバエの腸内細菌に対する免疫応答と寛容の分子機構2015

    • Author(s)
      柴田俊生
    • Organizer
      日本炎症・再生医学会
    • Place of Presentation
      東京都
    • Year and Date
      2015-07-21
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 脂質修飾によるトランスグルタミナーゼの局在化の制御機構2015

    • Author(s)
      柴田俊生、羽田野仁喜、関原早苗、小柴琢己、川畑俊一郎
    • Organizer
      日本生体防御学会
    • Place of Presentation
      東京都
    • Year and Date
      2015-07-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腸内細菌に対する免疫寛容による腸管恒常性維持2014

    • Author(s)
      柴田俊生、関原早苗、槇光輝、藤川匠、宮地隆太、石原健、小柴琢己、川畑俊一郎
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都市
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] ショウジョウバエの腸内細菌に対する免疫応答と寛容の分子機構2014

    • Author(s)
      柴田俊生、関原早苗、藤川匠、槇光輝、宮地隆太、石原健、小柴琢己、川畑俊一郎
    • Organizer
      第25回日本生体防御学会学術総会・日本比較免疫学会第26回学術集会合同学会
    • Place of Presentation
      仙台市
    • Year and Date
      2014-07-09 – 2014-07-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Transglutaminase-Catalyzed Protein-Protein Crosslinking Maintains the Gut Epithelial Immunity2014

    • Author(s)
      Toshio Shibata, Sanae Sekihara, Takumi Fujikawa, Ryuta Miyaji, Kouki Maki, Takeshi Ishihara, Takumi Koshiba, Shun-ichiro Kawabata
    • Organizer
      Gordon Research Conference, Transglutaminases in Human Disease Processes
    • Place of Presentation
      Lucca, Italy
    • Year and Date
      2014-06-29 – 2014-07-04
    • Related Report
      2014 Research-status Report
  • [Presentation] ショウジョウバエ自然免疫の応答制御と腸内細菌の共生成立の分子機構2014

    • Author(s)
      柴田俊生、関原早苗、槇光輝、藤川匠、宮地隆太、石原健、小柴琢己、川畑俊一郎
    • Organizer
      平成26年度日本生化学会九州支部例会シンポジウム
    • Place of Presentation
      福岡市
    • Year and Date
      2014-05-17 – 2014-05-18
    • Related Report
      2014 Research-status Report
    • Invited
  • [Book] Transglutaminases: Multiple Functional Modifiers and Targets for New Drug Discovery2015

    • Author(s)
      Toshio Shibata, Shun-ichiro Kawabata
    • Total Pages
      392
    • Publisher
      Springer Japan
    • Related Report
      2015 Annual Research Report
  • [Book] Transglutaminases: Multiple functional modifiers and targets for new drug discovery2015

    • Author(s)
      Toshio Shibata, Shun-ichiro Kawabata
    • Publisher
      Springer
    • Related Report
      2014 Research-status Report
  • [Remarks] 九州大学理学研究院生物科学部門生体高分子学研究室webページ

    • URL

      http://www.biology.kyushu-u.ac.jp/~biopoly/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 九州大学プレスリリース

    • URL

      http://www.kyushu-u.ac.jp/pressrelease/2014/2014_09_11.pdf

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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