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Recognition of compartment by microglia and its regulation of Scrap&Build

Planned Research

Project AreaDynamic regulation of brain function by Scrap & Build system
Project/Area Number 16H06458
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 InstitutionKyoto University

Principal Investigator

Suzuki Jun  京都大学, 高等研究院, 教授 (30511894)

Project Period (FY) 2016-06-30 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥79,430,000 (Direct Cost: ¥61,100,000、Indirect Cost: ¥18,330,000)
Fiscal Year 2020: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2019: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
Fiscal Year 2018: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2017: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2016: ¥22,230,000 (Direct Cost: ¥17,100,000、Indirect Cost: ¥5,130,000)
Keywords神経細胞 / コンパトーメンと / 除去 / スクリーニング / Phospholipid scrambling / neuron / synapse / engulfment / behavior / 神経 / スクランブラーゼ / 活性化因子 / sgRNA library / ホスファチジルセリン / FACS / 次世代シークエンサー / ニューロン / ミクログリア / 貪食 / "Eat-me" signal / cDNA library / レトロウイルス / Xkr / 細胞膜 / リン脂質 / シナプス / "eat me" signal / アストロサイト
Outline of Final Research Achievements

In this study, we investigated the scrap-and-build mechanism of neurons in the brain. Particularly we focused on the elimination mechanism of unwanted compartments in living neurons. We started to analyze the activation mechanism of scramblase Xkr4, which is specifically expressed in neurons. We developed a screening system using CRISPR sgRNA library, which we call revival screening. This system enables identification of factors even in non-proliferating or dying cells, and we identified the nuclear factor XRCC4 as its activation factor. XRCC4 is released into the cytoplasm when cleaved by caspases, and binds to and activates Xkr4. Xkr4 knockout mice were also analyzed and found to exhibit behavioral abnormalities.

Academic Significance and Societal Importance of the Research Achievements

本研究では神経細胞の不要コンパートメント除去機構の一端を明らかにした。生体内では常に不要細胞が除去され新しい細胞が生み出されている。また、神経細胞においては生きた細胞のコンパートメントが除去され、恒常性を維持している。我々は特に、不要な物質の除去という簡単から研究を進め、当分野に貢献した。本研究により、不要コンパートメントの除去の破綻は、発達障害様の行動異常を示すことが示唆されたことから、どの神経細胞のどのコンパートメントが除去されないとそのような病態を引き起こすのか今後研究することで、発達障害の発症機構の解明に寄与することがきできると考える。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (26 results)

All 2020 2019 2018 2017 2016

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (23 results) (of which Int'l Joint Research: 8 results,  Invited: 20 results)

  • [Journal Article] 細胞膜リン脂質スクランブリングの分子機構2019

    • Author(s)
      鈴木 淳
    • Journal Title

      医学のあゆみ

      Volume: 269 Pages: 1051-1054

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of the scrambling domain of the TMEM16 family2017

    • Author(s)
      Gyobu Sayuri、Ishihara Kenji、Suzuki Jun、Segawa Katsumori、Nagata Shigekazu
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 114 Issue: 24 Pages: 6274-6279

    • DOI

      10.1073/pnas.1703391114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Xkr8 phospholipid scrambling complex in apoptotic phosphatidylserine exposure2016

    • Author(s)
      Suzuki J, Imanishi E, Nagata S.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 113 Issue: 34 Pages: 9509-9514

    • DOI

      10.1073/pnas.1610403113

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 細胞膜脂質動態の制御機構並びにその応用2020

    • Author(s)
      鈴木 淳
    • Organizer
      AMED脂質領域会議
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 細胞膜脂質動態の異常による神経疾患発症の理解並びにその治療戦略の提案2020

    • Author(s)
      鈴木 淳
    • Organizer
      AMED-FORCEグループ会議
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Unbiased screening-based biology2020

    • Author(s)
      鈴木 淳
    • Organizer
      WPI-ASHBi Retreat
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Unbiased screening-based exploration of biological phenomenon ~lipid scrambling~2020

    • Author(s)
      鈴木 淳
    • Organizer
      第13回ABCセミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Unbiased screening-based understanding of lipid dynamics2020

    • Author(s)
      鈴木 淳
    • Organizer
      第24回細胞生理学セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 細胞膜脂質動態の異常による神経疾患発症の理解並びにその治療戦略の提案2019

    • Author(s)
      鈴木 淳
    • Organizer
      AMED-FORCE領域会議
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] On-site lab in Academia Sinica -with iCeMS Taiwan Office-2019

    • Author(s)
      Jun Suzuki
    • Organizer
      Kyoto University-Academia Sinica Bilateral Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] iCeMS Taiwan Office2019

    • Author(s)
      Jun Suzuki
    • Organizer
      NCKU-iCeMS-ASHBi-joint Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] On-site lab in Academia Sinica -with iCeMS Taiwan Office-2019

    • Author(s)
      Jun Suzuki
    • Organizer
      Kyoto University International Symposium on Education and Researchin Grobal Environemntal Studies in Asia
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Phospholipid scrambling on plasma membranes2019

    • Author(s)
      Jun Suzuki
    • Organizer
      1st Research Meeting on Cell Dynamics
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Unbiased screening-based exploration of biological phenomenon2019

    • Author(s)
      Jun Suzuki
    • Organizer
      IBMS Seminar
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanisms of phospholipid scrambling on plasma membranes2019

    • Author(s)
      鈴木 淳
    • Organizer
      日本生化学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ”Eat-me signal”-mediated Scrap & Build2019

    • Author(s)
      鈴木 淳
    • Organizer
      Scrap & Build Meeting
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 細胞膜脂質動態の制御機構並びにその応用2019

    • Author(s)
      鈴木 淳
    • Organizer
      AMED-PRIME領域会議
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Cellular and molecular sensing by the scramblase2019

    • Author(s)
      Jun Suzuki
    • Organizer
      Academia Sinica /Kyoto University bilateral symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanisms of lipid scrambling at intracellular organelles2019

    • Author(s)
      鈴木 淳
    • Organizer
      小野財団シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Phospholipid scrambling on the plasma membranes,2018

    • Author(s)
      Jun Suzuki
    • Organizer
      The SPIRITS Symposium: Multi-disciplinary approaches for cell control
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular Mechanisms of exposing “Eat-me” signal on the cell surface,2017

    • Author(s)
      鈴木 淳
    • Organizer
      日本細胞生物学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] アポトーシス時のリン脂質スクランブル2017

    • Author(s)
      鈴木 淳
    • Organizer
      Cell Death学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Phospholipid scrambling -lesson from mutants-2017

    • Author(s)
      鈴木 淳
    • Organizer
      CONBIO2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 細胞膜におけるリン脂質スクランブル-分子同定から機能解析まで-2017

    • Author(s)
      鈴木 淳
    • Organizer
      Advanced Seminar
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Phospholipid-scrambling proteins on the plasma membranes2017

    • Author(s)
      Jun Suzuki
    • Organizer
      Bangarol Life Science Cluster-iCeMS Joint Meeting.
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanism of phospholipid scrambling during apoptosis.2016

    • Author(s)
      鈴木 淳、長田 重一
    • Organizer
      日本生化学会大会
    • Related Report
      2016 Annual Research Report
    • Invited

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Published: 2016-07-04   Modified: 2023-01-30  

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