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Regulation mechanisms of receptor activity by glycolipids as revealed by high-resolution single-molecule imaging

Research Project

Project/Area Number 18H02401
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionGifu University

Principal Investigator

Suzuki Kenichi  岐阜大学, 糖鎖生命コア研究所, 教授 (50423059)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywordsガングリオシド / ラフト / 1分子観察 / 糖鎖 / ダイマー / 1分子観察 / 脂質ラフト / シグナル伝達 / 膜受容体 / 糖脂質 / GPIアンカー型タンパク質 / 細胞膜ドメイン
Outline of Final Research Achievements

We synthesized new ganglioside probes which partitioned into raft fraction. Single-fluorescent molecule imaging of these new ganglioside probes revealed that 1) all the observed gangliosides formed transient homodimers, 2) the ganglioside homodimers were formed by the specific glycan-glycan interactions, 3) the ganglioside homodimers transiently recruited other raftophilic molecules, and formed tiny rafts. Furthermore, 4) the homodimer formation of gangliosides by specific glycan-glycan interactions was supported by the all-atom molecular dynamics simulations, and we revealed that 5) dimerization and activation of EGF receptors are inhibited by the specific glycan-glycan interactions of GM3 homodimers with N-glycans of EGF receptors.

Academic Significance and Societal Importance of the Research Achievements

糖鎖―糖鎖相互作用は、異なる膜間や同じタンパク質上では定量的に調べられてきたが、同じ膜の側方(シス)方向で存在するかどうか長い間議論があった。我々は高精度1分子観察法を用いた本研究により、糖鎖―糖鎖相互作用が、細胞膜分子の組織化に非常に重要な役割を担っていることを示すことができた。糖鎖―糖鎖相互作用は、EGF受容体以外でも、様々な受容体の活性制御において機能しているかもしれず、今後の研究が期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (38 results)

All 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 5 results) Presentation (24 results) (of which Int'l Joint Research: 5 results,  Invited: 16 results) Book (2 results)

  • [Journal Article] One-pot construction of microcomponent supramolecular materials comprising self-sorted supramolecular architechtures of DNA and semi-artificial g;ycopeptides.2020

    • Author(s)
      S. L. Higashi, K. M. Hirosawa, K. G. N. Suzuki, K. Matsuura, M. Ikeda.
    • Journal Title

      ACS Applied Biomaterials

      Volume: 30 Issue: 12 Pages: 9082-9092

    • DOI

      10.1021/acsabm.0c01316

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-speed single-molecule imaging reveals signal transduction by onduced transbilayer raft phases.2020

    • Author(s)
      I. Koyama-Honda, T. K. Fujiwara, R. S. Kasai, K. G. N. Suzuki, E. Kajikawa, T. A. Tsunoyama, A. Kusumi.
    • Journal Title

      J. Cell Biol.

      Volume: 219 Issue: 12

    • DOI

      10.1083/jcb.202006125

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of Fluorescent Ganglioside GD3 and GQ1b Analogs for Elucidation of Raft-Associated Interactions2020

    • Author(s)
      M. Konishi, N. Komura, Y. Hirose, Y. Suganuma, H. N. Tanaka, A. Imamura, H. Ishida, K. G. N. Suzuki*, H. Ando*
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 85 Issue: 24 Pages: 15998-16013

    • DOI

      10.1021/acs.joc.0c01493

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic actin-mediated nano-scale clustering of CD44 regulates its meso-scale organization at the plasma membrane2019

    • Author(s)
      P. Sil, N. Mateos, S. Nath, S. Buschow, C. Manzo, K.G.N. Suzuki, T. Fujiwara, A. Kusumi, M.F. Garcia-Parajo, and S. Mayor
    • Journal Title

      Mol. Biol. Cell

      Volume: 31 Issue: 7 Pages: 561-579

    • DOI

      10.1091/mbc.e18-11-0715

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Defining raft domains in the plasma membrane2019

    • Author(s)
      Akihiro Kusumi、Takahiro K. Fujiwara、Taka A. Tsunoyama、Rinshi S. Kasai、An‐An Liu、Koichiro M. Hirosawa、Masanao Kinoshita、Nobuaki Matsumori、Naoko Komura、Hiromune Ando、Kenichi G. N. Suzuki
    • Journal Title

      Traffic

      Volume: 21 Issue: 1 Pages: 106-137

    • DOI

      10.1111/tra.12718

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of fluorescently labeled SSEA-3, SSEA-4 and Globo-H glycosphingolipids for elucidating molecular interactions in the cell membrane.2019

    • Author(s)
      Sachi Asano, Rita Pal, Hide-Nori Tanaka, Akihiro Imamura, Hideharu Ishida, Kenichi G.N. Suzuki*, Hiromune Ando*(*corresponding author).
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 24 Pages: 6187-6187

    • DOI

      10.3390/ijms20246187

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] AMPA receptors in the synapse turnover by monomer diffusion.2019

    • Author(s)
      Morise J, Suzuki K, Kitagawa A, Wakazono Y, Takamiya K, Tsunoyama T, Nemoto Y, Takematsu H, Kusumi A, Oka S.
    • Journal Title

      Nat. Commun.

      Volume: 10 Issue: 1 Pages: 5245-5245

    • DOI

      10.1038/s41467-019-13229-8

    • NAID

      120006769184

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hybrid soft nanomaterials composed of DNA microspheres and supermolecular nanostructures of semi-artificial glycopeptides.2019

    • Author(s)
      Sayuri L. Higashi, Aya Shibata, Yoshiaki Kitamura, Koichiro M. Hirosawa, Kenichi G. N. Suzuki, Kazunori Matsuda, Masato Ikeda.
    • Journal Title

      Chemistry

      Volume: 25 Issue: 51 Pages: 11955-11962

    • DOI

      10.1002/chem.201902421

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual-FRET imaging of IP3 and Ca2+ revealed Ca2+-induced IP3 production maintains long lasting Ca2+ oscillations in fertilized mouse eggs.2019

    • Author(s)
      Toru Mitsu-Ura, Hideki Shirakawa, Kenichi G. N. Suzuki, Akitoshi Miyamoto, Kotomi Sugiura, Takayuki Michikawa, Akihiro Kusumi, Katsuhiko Mikoshiba.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 4829-4829

    • DOI

      10.1038/s41598-019-40931-w

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unraveling of lipid raft organization in cell plasma membranes by single-molecule imaging of ganglioside probes.2018

    • Author(s)
      Kenichi G. N. Suzuki, Hiromune Ando, Naoko Komura, Takahiro Fujiwara, Makoto Kiso, Akihiro Kusumi.
    • Journal Title

      Advances in Experimental Medicine and Biology

      Volume: 1104 Pages: 41-58

    • DOI

      10.1007/978-981-13-2158-0_3

    • ISBN
      9789811321573, 9789811321580
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evidence of lipid rafts based on the partition and dynamic behavior of sphingomyelins2018

    • Author(s)
      Kinoshita Masanao、Suzuki Kenichi G.N.、Murata Michio、Matsumori Nobuaki
    • Journal Title

      Chemistry and Physics of Lipids

      Volume: 215 Pages: 84-95

    • DOI

      10.1016/j.chemphyslip.2018.07.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Super-long single-molecule tracking reveals dynamic-anchorage-induced integrin function.2018

    • Author(s)
      Takaaki A. Tsunoyama, Yusuke Watanabe, Junri Goto, Kazuma Naito, Rinshi S. Kasai, Kenichi G. N. Suzuki, Takahiro K. Fujiwara, Akihiro Kusumi.
    • Journal Title

      Nature Chemical Biology

      Volume: 14 Issue: 5 Pages: 497-506

    • DOI

      10.1038/s41589-018-0032-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] リアルタイム超解像動画観察による形質膜内層脂質ドメインの共局在解析2021

    • Author(s)
      森俊貴、廣澤幸一朗、田口友彦、横田康成、鈴木健一
    • Organizer
      令和2年度 日本生物物理学会中部支部講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 細胞外小胞の標的細胞への結合制御:1粒子解析法による解明2021

    • Author(s)
      磯貝 樹、廣澤 幸一朗、木塚 康彦、横田 康成、鈴木 健一
    • Organizer
      令和2年度 日本生物物理学会中部支部講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 単粒子追跡法と超解像顕微鏡法を用いたエクソソーム粒子の標的細胞への取り込み機構の解明2021

    • Author(s)
      廣澤幸一朗、横田康成、鈴木健一
    • Organizer
      令和2年度 日本生物物理学会中部支部講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 高精度1分子観察によるラフト組織化と機能の解明2021

    • Author(s)
      鈴木健一
    • Organizer
      生物工学・脂質駆動学術産業創生研究部会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 糖鎖による細胞外小胞の標的細胞への結合制御:1粒子解析法による解明2021

    • Author(s)
      磯貝樹、廣澤幸一朗、木塚康彦、横田康成、鈴木健一
    • Organizer
      糖鎖科学中部拠点 第16回 「若手の力」フォーラム
    • Related Report
      2020 Annual Research Report
  • [Presentation] 生細胞での超解像・1分子可視化解析による標的細胞におけるエクソソーム取り込み機構の解明2021

    • Author(s)
      廣澤幸一朗、磯貝樹、木塚康彦、横田康成、鈴木健一
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 高精度1分子で明らかになったラフト組織化と機能2020

    • Author(s)
      鈴木健一
    • Organizer
      分子夾雑化学東海地区シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Regulation of exosome function by glycans as revealed by single-molecule imaging2020

    • Author(s)
      Tatsuki Isogai, Koichiro M. Hirosawa, Yasuhiko Kizuka, Yasunari Yokoto, Kenichi G. N. Suzuki
    • Organizer
      第58回日本生物物理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Raft organization and function as revealed by single-molecule imaging2020

    • Author(s)
      鈴木健一
    • Organizer
      第58回日本生物物理学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] エクソソーム膜動態の超解像・1分子可視化解析2020

    • Author(s)
      鈴木健一
    • Organizer
      日本分析化学会第69年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 1分子観察によるガングリオシド会合機構とEGF受容体化成制御機構の解明2020

    • Author(s)
      鈴木健一
    • Organizer
      日本農芸化学会2020大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] N型糖鎖によるエクソソームの取り込み制御機構の解明2020

    • Author(s)
      磯貝樹、廣澤幸一朗、木塚康彦、鈴木健一
    • Organizer
      日本農芸化学会2020大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] エクソソーム膜動態の1分子可視化解析2019

    • Author(s)
      鈴木健一
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 1分子イメージングによるエクソソーム膜動態の解明2019

    • Author(s)
      鈴木健一
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Uptake mechanism of exosomes on the recipient cells: Superresolution and single particle tracking study2019

    • Author(s)
      Koichiro M. Hirosawa, Takaaki A. Tsunoyama, Yasunari Yokota, Kenichi G.N. Suzuki
    • Organizer
      The 57th Annual Meeting of the Biophysical Society of Japan
    • Related Report
      2019 Annual Research Report
  • [Presentation] Regulation mechanisms of EGF receptors by gangliosides as revealed by single-molecule imaging2019

    • Author(s)
      Kenichi G.N. Suzuki
    • Organizer
      1st japan-Europe Workshop on Glycosphingolipids and Membrane Homeastasis
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Single-molecule imaging study of regulation mechanisms of EGF receptor activity by gangliosides2019

    • Author(s)
      Kenichi G.N. Suzuki
    • Organizer
      Glyco25
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulation mechanisms of EGF receptor activation by gangliosides as revealed by single-molecule imaging2019

    • Author(s)
      Kenichi G.N. Suzuki
    • Organizer
      60th International Conference on the Bioscience of Lipids
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Single-molecule imaging study of dynamics of rafts and exosomes2019

    • Author(s)
      Kenichi G.N. Suzuki
    • Organizer
      International symposium on Bio-chains from single molecules to highly organized systems
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 高精度1分子観察によるラフト組織化と機能の解明2019

    • Author(s)
      鈴木健一
    • Organizer
      第66回脳の医学・生物学研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Regulation mechanisms of EGFR activity by gangliosides as revealed by single-molecule imaging.2018

    • Author(s)
      Kenichi Suzuki
    • Organizer
      JAACT2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulation mechanisms of EGFR activity by ganglioside homodimer rafts as revealed by single-molecule imaging.2018

    • Author(s)
      Kenichi Suzuki
    • Organizer
      The 56th Annual Meeting of the Biophysical Society of Japan.
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 高精度1分子観察によるラフト組織化とシグナル制御機構の解明2018

    • Author(s)
      鈴木健一
    • Organizer
      第40回日本生物学的精神医学会・第61回日本神経化学会大会 合同年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 細胞膜の組織化と機能:高精度1分子観察による解明2018

    • Author(s)
      鈴木健一
    • Organizer
      第19回運動器科学研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] 膜タンパク質工学ハンドブック 第1編 膜タンパク質の基礎 第2章 構造・物性・分析・解析 第17節 1分子計測2020

    • Author(s)
      鈴木健一
    • Total Pages
      7
    • Publisher
      エヌ・ティー・エス
    • ISBN
      9784860435370
    • Related Report
      2019 Annual Research Report
  • [Book] The Lipid 見る脂質のページ 第3回1分子観察によるラフト組織化と機能の解明2020

    • Author(s)
      鈴木健一
    • Total Pages
      6
    • Publisher
      メデイカルレビュー社
    • ISBN
      9784779223860
    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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