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The new aspects of lysosomal signal regulation by Ragulator

Research Project

Project/Area Number 20K06623
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionOsaka University

Principal Investigator

Nada Shigeyuki  大阪大学, 微生物病研究所, 准教授 (50291448)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsmTORC1 / Ragulator / Lamtor1 / p18 / Rab7 / Gator1 / goblet cell / DEPDC5 / PP2A / リソソーム
Outline of Research at the Start

リソソーム膜上のタンパク質複合体であるRagulatorは、mTORC1の機能調節に加え様々な因子との相互作用することで、細胞の代謝調節を行うリソソームシグナルの重要な起点となっている。この研究ではその機能の一端として、マウス腸上皮杯細胞の分化におけるRagulatorの生理的役割を解明し、またmTORC1活性調節におけるアミノ酸調節経路との相互作用の場としての役割を明らかにするための解析を行う。

Outline of Final Research Achievements

Ragulator is an important component for mTORC1 regulation. In this study the physiological function of Ragulator in intestinal epithelium was evaluated by use of conditional knockout mice. The results showed that Ragulator is essential for the development of intestinal epithelium, especially for goblet cell function. In addition, knockout cell studies revealed that the structure of Ragulator is indispensable for amino-acid regulation of mTORC1 activation.

Academic Significance and Societal Importance of the Research Achievements

この研究はmTORC1活性調節の中でもRagulatorに関する部分に焦点を当てたものである。mTORC1研究は国内外に多数あるが、Ragulatorに関しては我々が同定し機能を明らかにしてきた。当研究もその一翼を担うものであり、mTORC1の調節と機能に関する新たな知見を提供できたものと考える。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (15 results)

All 2023 2022 2021 2020

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 7 results) Presentation (6 results) (of which Invited: 1 results)

  • [Journal Article] A TGF-β-responsive enhancer regulates SRC expression and epithelial?mesenchymal transition-associated cell migration2023

    • Author(s)
      Noshita Soshi、Kubo Yuki、Kajiwara Kentaro、Okuzaki Daisuke、Nada Shigeyuki、Okada Masato
    • Journal Title

      Journal of Cell Science

      Volume: 136 Issue: 15

    • DOI

      10.1242/jcs.261001

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The lysosomal Ragulator complex activates NLRP3 inflammasome in vivo via HDAC6.2023

    • Author(s)
      Tsujimoto K, Jo T, Nagira D, Konaka H, Park JH, Yoshimura SI, Ninomiya A, Sugihara F, Hirayama T, Itotagawa E, Matsuzaki Y, Takaichi Y, Aoki W, Saita S, Nakamura S, Ballabio A, Nada S, Okada M, Takamatsu H, Kumanogoh A.
    • Journal Title

      EMBO J.

      Volume: 42 Issue: 1

    • DOI

      10.15252/embj.2022111389

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SRC kinase activator CDCP1 promotes hepatocyte growth factor-induced cell migration/invasion of a subset of breast cancer cells2022

    • Author(s)
      Kawase Naoyuki、Sugihara Atsuya、Kajiwara Kentaro、Hiroshima Michio、Akamatsu Kanako、Nada Shigeyuki、Matsumoto Kunio、Ueda Masahiro、Okada Masato
    • Journal Title

      Journal of Biological Chemistry

      Volume: 298 Issue: 3 Pages: 101630-101630

    • DOI

      10.1016/j.jbc.2022.101630

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Ragulator complex serves as a substrate-specific mTORC1 scaffold in regulating the nuclear translocation of transcription factor EB2022

    • Author(s)
      Kimura Tetsuya、Hayama Yoshitomo、Okuzaki Daisuke、Nada Shigeyuki、Okada Masato
    • Journal Title

      Journal of Biological Chemistry

      Volume: 298 Issue: 3 Pages: 101744-101744

    • DOI

      10.1016/j.jbc.2022.101744

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] d-Serine Mediates Cellular Proliferation for Kidney Remodeling2021

    • Author(s)
      Hesaka Atsushi、Tsukamoto Yusuke、Nada Shigeyuki、Kawamura Masataka、Ichimaru Naotsugu、Sakai Shinsuke、Nakane Maiko、Mita Masashi、Okuzaki Daisuke、Okada Masato、Isaka Yoshitaka、Kimura Tomonori
    • Journal Title

      Kidney360

      Volume: 2 Issue: 10 Pages: 1611-1624

    • DOI

      10.34067/kid.0000832021

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] β-catenin-promoted cholesterol metabolism protects against cellular senescence in naked mole-rat cells2021

    • Author(s)
      Chee Woei-Yaw、Kurahashi Yuriko、Kim Junhyeong、Miura Kyoko、Okuzaki Daisuke、Ishitani Tohru、Kajiwara Kentaro、Nada Shigeyuki、Okano Hideyuki、Okada Masato
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 357-357

    • DOI

      10.1038/s42003-021-01879-8

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The lysosomal Ragulator complex plays an essential role in leukocyte trafficking by activating myosin II2021

    • Author(s)
      Nakatani Takeshi、Tsujimoto Kohei、Park JeongHoon、Jo Tatsunori、Kimura Tetsuya、Hayama Yoshitomo、Konaka Hachiro、Morita Takayoshi、Kato Yasuhiro、Nishide Masayuki、Koyama Shyohei、Nada Shigeyuki、Okada Masato、Takamatsu Hyota、Kumanogoh Atsushi
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 3333-3333

    • DOI

      10.1038/s41467-021-23654-3

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic dissection of Ragulator structure and function in amino acid-dependent regulation of mTORC12020

    • Author(s)
      Nada Shigeyuki、Okada Masato
    • Journal Title

      The Journal of Biochemistry

      Volume: 168 Issue: 6 Pages: 621-632

    • DOI

      10.1093/jb/mvaa076

    • NAID

      40022454691

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] p18/Lamtor1-mTORC1 Signaling Controls Development of Mucin-producing Goblet Cells in the Intestine2020

    • Author(s)
      Ito Shizuka、Nada Shigeyuki、Yamazaki Daisuke、Kimura Tetsuya、Kajiwara Kentaro、Miki Hiroaki、Okada Masato
    • Journal Title

      Cell Structure and Function

      Volume: 45 Issue: 2 Pages: 93-105

    • DOI

      10.1247/csf.20018

    • NAID

      130007871371

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Ragulator and the surrounding system for mTORC1 regulation2021

    • Author(s)
      名田 茂之、岡田 雅人
    • Organizer
      第44回日本分子生物学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] がん微小環境におけるがん原遺伝子Src活性化意義の解明2021

    • Author(s)
      冨嶋 佳乃、名田 茂之、岡田 雅人
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 発がん段階におけるがん遺伝子Srcと制御因子Cskの意義2021

    • Author(s)
      野村 優斗、名田 茂之、岡田 雅人
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Research-status Report
  • [Presentation] アミノ酸によるmTORC1活性調節におけるRagulator構造の意義2020

    • Author(s)
      名田 茂之、岡田 雅人
    • Organizer
      227.第93回 日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] アミノ酸依存的mTORC1栄養シグナルの制御と機能2020

    • Author(s)
      名田 茂之、伊藤 静夏、山崎 大輔、三木 裕明、岡田 雅人
    • Organizer
      229.第93回 日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] アミノ酸によるmTORC1活性調節はRagulator構造に依存する2020

    • Author(s)
      名田 茂之、岡田 雅人
    • Organizer
      230.第43回 日本分子生物学会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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