Regulation mechanisms of receptor activity by glycolipids as revealed by high-resolution single-molecule imaging
| Project/Area Number |
18H02401
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 43030:Functional biochemistry-related
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| Research Institution | Gifu University |
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Principal Investigator |
Suzuki Kenichi 岐阜大学, 糖鎖生命コア研究所, 教授 (50423059)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(38 results)
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[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
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Journal Title
Traffic
Volume: 21
Issue: 1
Pages: 106-137
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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