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Study on the amino acid-sensing and the activity regulation mechanisms of TORC1 using a novel in vitro assay system

Research Project

Project/Area Number 17H03802
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied biochemistry
Research InstitutionHamamatsu University School of Medicine (2018-2019)
The University of Tokyo (2017)

Principal Investigator

Maeda Tatsuya  浜松医科大学, 医学部, 教授 (90280627)

Co-Investigator(Kenkyū-buntansha) 藤木 克則  東京大学, 定量生命科学研究所, 助教 (10646730)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywordsシグナル伝達 / TOR / TORC1 / グルタミン
Outline of Final Research Achievements

In the Pib2 pathway, which is the Gtr/Rag-independent glutamine-responsive TORC1 activation mechanism in yeast, the vacuolar protein Pib2 changes its structure upon biding to glutamine and thereby binds to and activates TORC1. In addition, the glutamine-responsive TORC1 activation was reconstituted in vitro solely using Pib2 and TORC1. These observations indicate that Pib2 is the glutamine sensor as well as the direct activator of TORC1 in the Pib2 pathway.

Academic Significance and Societal Importance of the Research Achievements

TORC1は代謝を制御する主要なシグナル伝達因子で、さまざま疾患の発症・増悪に関与しており、その制御機構の解明が待たれている。アミノ酸を検知してTORC1を活性化する機構について、不明な点の多かったGtr/Rag非依存性・グルタミン応答性の分子機構を初めて明らかにした。この機構は多くの生物種を通じて広く保存されている可能性がある。また、細胞内に高濃度で存在する代謝物を特異的に検知する機構としての一般性を備えている。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (35 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (3 results) Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (22 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (2 results)

  • [Int'l Joint Research] University of Basel(スイス)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Orleans/University of Tours(フランス)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Illinois(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] TORC1 regulates autophagy induction in response to proteotoxic stress in yeast and human cells2019

    • Author(s)
      Kazuki Suda, Atsuki Kaneko, Mitsugu Shimobayashi, Akio Nakashima, Tatsuya Maeda, Michael N Hall, Takashi Ushimaru
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 511 Issue: 2 Pages: 434-439

    • DOI

      10.1016/j.bbrc.2019.02.077

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] New Insight into HPts as Hubs in Poplar Cytokinin and Osmosensing Multistep Phosphorelays: Cytokinin Pathway Uses Specific HPts2019

    • Author(s)
      Hericourt Francois、Larcher Melanie、Chefdor Francoise、Koudounas Konstantinos、Carqueijeiro Ines、Lemos Cruz Pamela、Courdavault Vincent、Tanigawa Mirai、Maeda Tatsuya、Depierreux Christiane、Lamblin Frederic、Glevarec Gaelle、Carpin Sabine
    • Journal Title

      Plants

      Volume: 8 Issue: 12 Pages: 591-591

    • DOI

      10.3390/plants8120591

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hyperactivation of mTORC1 disrupts cellular homeostasis in cerebellar Purkinje cells2019

    • Author(s)
      Sakai Y, Kassai H, Nakayama H, Fukaya M, Maeda T, Nakao K, Hashimoto K, Sakagami H, Kano M, Aiba A.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 2799-2799

    • DOI

      10.1038/s41598-019-38730-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Helicobacter pylori Infection Modulates Host Cell Metabolism through VacA-Dependent Inhibition of mTORC12018

    • Author(s)
      Kim Ik-Jung、Lee Jeongmin、Oh Seung J.、Yoon Mee-Sup、Jang Sung-Soo、Holland Robin L.、Reno Michael L.、Hamad Mohammed N.、Maeda Tatsuya、Chung Hee Jung、Chen Jie、Blanke Steven R.
    • Journal Title

      Cell Host & Microbe

      Volume: 23 Issue: 5 Pages: 583-593.e8

    • DOI

      10.1016/j.chom.2018.04.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Serine phosphorylation by mTORC1 promotes IRS-1 degradation through SCF-b-TRCP E3 ubiquitin ligase2018

    • Author(s)
      Yoneyama Y, Inamitsu T, Chida K, Iemura SI, NatsumeT, Maeda T, Hakuno F, Takahashi S-I
    • Journal Title

      iScience

      Volume: 5 Pages: 1-18

    • DOI

      10.1016/j.isci.2018.06.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nutrient signaling via the TORC1-greatwall-PP2AB55δ pathway is responsible for the high initial rates of alcoholic fermentation in sake yeast strains of Saccharomyces cerevisiae.2018

    • Author(s)
      D. Watanabe, T. Kajihara, Y. Sugimoto, K. Takagi, M. Mizuno, Y. Zhou, J. Chen, K. Takeda, H. Tatebe, K. Shiozaki, N. Nakazawa, S. Izawa, T. Akao, H. Shimoi, T. Maeda, and H. Takagi
    • Journal Title

      Appl. Environ. Microbiol.

      Volume: 85 Issue: 1

    • DOI

      10.1128/aem.02083-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An In Vitro TORC1 Kinase Assay That Recapitulates the Gtr-Independent Glutamine-Responsive TORC1 Activation Mechanism on Yeast Vacuoles2017

    • Author(s)
      Mirai Tanigawa、Tatsuya Maeda
    • Journal Title

      Mol Cell Biol

      Volume: 37 Issue: 14

    • DOI

      10.1128/mcb.00075-17

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hyperactive mTOR induces neuroendocrine differentiation in prostate cancer cell with concurrent up-regulation of IRF12017

    • Author(s)
      Kanayama Mayuko、Hayano Toshiya、Koebis Michinori、Maeda Tatsuya、Tabe Yoko、Horie Shigeo、Aiba Atsu
    • Journal Title

      Prostate

      Volume: 77 Issue: 15 Pages: 1489-1498

    • DOI

      10.1002/pros.23425

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] TORC1経路における細胞内グルタミン検知機構2020

    • Author(s)
      谷川美頼、山本勝良、前田達哉
    • Organizer
      日本農芸化学会 2020年度(令和2年度)大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 酵母のグルタミン検知に関与する天然変性タンパク質Pib2の液滴形成2019

    • Author(s)
      前田達哉
    • Organizer
      第19回日本蛋白質科学会年会 第71回日本細胞生物学会 合同年次大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 出芽酵母スフィンゴ脂質代謝制御に関わる機能未知転写因子Mlm2の機能解析2019

    • Author(s)
      小松楠於、石野裕子、谷元洋、上野俊哉、前田達哉、 田中直孝、田淵光昭
    • Organizer
      酵母遺伝学フォーラム 第52回研究報告会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 細胞内グルタミン検知機構の解析2019

    • Author(s)
      谷川美頼、山本勝良、前田達哉
    • Organizer
      酵母遺伝学フォーラム 第52回研究報告会
    • Related Report
      2019 Annual Research Report
  • [Presentation] edelfosineを用いたTOR複合体2シグナル制御機構の解析2019

    • Author(s)
      野村亘、後藤剛、高原照直、前田達哉、井上善晴
    • Organizer
      酵母遺伝学フォーラム 第52回研究報告会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 酵母のグルタミン検知に関与する天然変性タンパク質Pib2の液滴形成2019

    • Author(s)
      前田達哉
    • Organizer
      大阪大学蛋白研セミナー/第3回LLPS研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 出芽酵母cell wall integrity経路が関わるTOR複合体2シグナル制御機構の解析2019

    • Author(s)
      野村亘、後藤剛、高原照直、前田達哉、河田照雄、井上善晴
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] mTORC1シグナル亢進による小脳プルキンエ細胞の細胞内ホメオスタシスの撹乱2019

    • Author(s)
      坂井祐介、葛西秀俊、中山寿子、深谷昌弘、前田達哉、中尾和貴、橋本浩一、阪上洋行、狩野方伸、饗場篤
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 細胞内グルタミン検知機構の解析2019

    • Author(s)
      谷川美頼、山本勝良、前田達哉
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 酵母TORC1経路のアミノ酸検知機構2019

    • Author(s)
      前田達哉
    • Organizer
      第86回酵母研究会講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Pib2によるTORC1活性化機構の解析2018

    • Author(s)
      谷川美頼、山本勝良、前田達哉
    • Organizer
      酵母遺伝学フォーラム第51回研究報告会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The glutamine-responsive TORC1 activation mechanism in yeast2018

    • Author(s)
      前田達哉
    • Organizer
      第13回プロテインホスファターゼ国際カンファレンス
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 酵母のグルタミン特異的 TORC1活性化機構2018

    • Author(s)
      谷川 美頼、山本 勝良、前田 達哉
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 酵母のアミノ酸検知機構―シグナルとしての栄養源2018

    • Author(s)
      前田達哉
    • Organizer
      大隅基礎科学創成財団 第4回創発セミナー
    • Related Report
      2018 Annual Research Report
  • [Presentation] Rag/Gtr非依存性・グルタミン応答性TORC1活性化機構2018

    • Author(s)
      前田達哉
    • Organizer
      反町洋之博士追悼記念シンポジウム―Three Decades of Calpain
    • Related Report
      2018 Annual Research Report
  • [Presentation] Pib2を介したTORC1活性化機構の解析2018

    • Author(s)
      谷川美頼、山本勝良、前田達哉
    • Organizer
      日本農芸化学会 2018年度(平成30年度)大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 酵母のアルコール発酵調節におけるTORC1シグナリングとアミノ酸の効果2018

    • Author(s)
      渡辺 大輔、杉本 幸子、水野 恵、周 延、陳 佳文、赤尾 健、下飯 仁、前田 達哉、高木 博史
    • Organizer
      日本農芸化学会 2018年度(平成30年度)大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] An in vitro TORC1 Kinase Assay that Recapitulates the Gtr-Independent Glutamine-responsive TORC1 Activation Mechanism on Yeast Vacuole2017

    • Author(s)
      Mirai Tanigawa
    • Organizer
      28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pib2を介したTORC1活性化機構の解析2017

    • Author(s)
      谷川美頼、前田達哉
    • Organizer
      酵母遺伝学フォーラム 第50回研究報告会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Cdc42が関与する出芽酵母TOR複合体2シグナルの解析2017

    • Author(s)
      野村 亘、後藤 剛、高原 照直、前田 達哉、河田 照雄、井上 善晴
    • Organizer
      酵母遺伝学フォーラム 第50回研究報告会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 小脳プルキンエ細胞における mTORC1シグナルの活性化は、プ ルキンエ細胞の細胞死および肥大化を引き起こす2017

    • Author(s)
      坂井 祐介、葛西 秀俊、中山 寿子、前田 達哉、中尾 和貴、橋本 浩一、狩野 方伸、饗場 篤
    • Organizer
      2017年度 生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] グルタミン特異的TORC1活性化機構2017

    • Author(s)
      谷川美頼、前田達哉
    • Organizer
      日本遺伝学会 第89回大会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 浜松医科大学 医学部 医学科 総合人間科学 生物学、教授 前田達哉

    • URL

      https://kenkyu-web.hama-med.ac.jp/Profiles/1/0000033/profile.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] Google Scholar, Tatsuya Maeda

    • URL

      https://scholar.google.co.jp/citations?user=3j7TygEAAAAJ&hl=ja&oi=ao

    • Related Report
      2019 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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