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Mechanism of Notch receptor signaling and its dependency on lipids

Research Project

Project/Area Number 21K06038
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43020:Structural biochemistry-related
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

Sato Takeshi  京都薬科大学, 薬学部, 教授 (90403013)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsNotchシグナリング / Context dependency / マイクロドメイン / context dependency / Notch / 生体膜 / 半合成 / 分子動力学計算 / Notch受容体 / Ligation / 膜タンパク質 / 情報伝達 / 固体NMR
Outline of Research at the Start

Notch受容体の機能発現にはcotext dependencyが存在するとされる。それは何らかのcontextに応じて、異なる遺伝子の活性化として観察される。その機構は未知であり、我々は脂質依存的なNotch受容体の構造、clusteringの差異がこのcontext dependencyを与えると考え、その機構の構造化学的解析を行う。

Outline of Final Research Achievements

One of the most scientifically interesting phenomena in Notch signaling is its "context dependency". This context dependency can be explained as follow: Notch ligands activate distinct target through the same receptor. In this project we decided to get insight on the molecular mechanism of this phenomenon.
We have worked on molecular dynamics on looking at Notch ligand and certain lipids and found that each kind of ligand has preference in binding for a certain lipid such as GM1 or GM3. This selectivity, or specificity, may explain the context dependency. "Wet" experiments are in progress to verify the validity of results from the MD simulation.

Academic Significance and Societal Importance of the Research Achievements

Notch受容体に関する基礎研究は発生学分野が中心となり、細胞生物学、生化学的研究が行われるようになった。疾患との関連も深く、医学、創薬的にも関心の高い研究対象であり、多くの研究がなされている。このシグナリングにおけるcontext dependency機構の解明は、受容体と脂質との協奏機構を解き明かす上で重要であり、本研究結果は今後の当該研究分野における道筋を示すものであると考えられる。

Report

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

    (6 results)

All 2023 2022 2021

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (1 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Characterizing interaction between the juxtamembrane region of the single transmembrane protein and membrane using chemically synthesized peptides2023

    • Author(s)
      Sato Takeshi、Shinohara Akira
    • Journal Title

      STAR Protocols

      Volume: 4 Issue: 3 Pages: 102454-102454

    • DOI

      10.1016/j.xpro.2023.102454

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of hydrophobic moment on membrane interaction and cell penetration of apolipoprotein E-derived arginine-rich amphipathic α-helical peptides.2022

    • Author(s)
      1)Yuki Takechi-Haraya, Takashi Ohgita, Mana Kotani, Hiroki Kono, Chihiro Saito, Hiroko Tamagaki-Asahina, Kazuchika Nishitsuji, Kenji Uchimura, Takeshi Sato, Ryuji Kawano, Kumiko Sakai-Kato, Ken-ichi Izutsu, Hiroyuki Saito
    • Journal Title

      Sci. Rep.

      Volume: 12 Pages: 4959-4959

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Threonine phosphorylation regulates the molecular assembly and signaling of EGFR in cooperation with membrane lipids.2022

    • Author(s)
      2)Ryo Maeda, Hiroko Tamagaki-Asahina, Takeshi Sato, Masataka Yanagawa, Yasushi Sako.
    • Journal Title

      J Cell Sci.

      Volume: 135 Issue: 15 Pages: 1-12

    • DOI

      10.1242/jcs.260355

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Total Synthesis and Structural Characterization of Caveolin-12021

    • Author(s)
      Hironobu Hojo, Toshiki Takei, Yuya Asahina, Nobuaki Okumura, Toshifumi Takao, Masatomo So, Isao Suetake, Takeshi Sato, Akihiro Kawamoto, Yoshio Hirabayashi
    • Journal Title

      Angew Chem Int Ed Engl .

      Volume: 60 Issue: 25 Pages: 13900-13905

    • DOI

      10.1002/anie.202100826

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of luminal region of the SUN-domain protein Mps3 promotes nuclear envelope localization during meiosis2021

    • Author(s)
      Prasada Rao Hanumanthu BD、Sato Takeshi、Challa Kiran、Fujita Yurika、Shinohara Miki、Shinohara Akira
    • Journal Title

      eLife

      Volume: 10 Pages: 1-29

    • DOI

      10.7554/elife.63119

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] What's going on in the membrane, activation mechanism of receptor tyrosine kinase2023

    • Author(s)
      Takeshi Sato
    • Organizer
      International Symposium at National Taiwan University, School of Pharmacy
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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