Functional Dynamics of Liquid-Liquid Phase Separation Mediated by Nuclear Pore Complex
| Project/Area Number |
21K19043
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 37:Biomolecular chemistry and related fields
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| Research Institution | Kanazawa University |
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Principal Investigator |
Wong Richard 金沢大学, ナノ生命科学研究所, 教授 (30464035)
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| Co-Investigator(Kenkyū-buntansha) |
小林 亜紀子 金沢大学, 新学術創成研究機構, 特任助教 (00345662)
羽澤 勝治 金沢大学, 新学術創成研究機構, 准教授 (40622460)
LIM KEE・SIANG 金沢大学, ナノ生命科学研究所, 特任助教 (60842987)
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| Project Period (FY) |
2021-07-09 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 核膜孔複合体 / 核膜孔 / 液－液相分離 / 翻訳後修飾 / 相分離 |
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| Outline of Research at the Start |
本研究は、高次遺伝子発現システムの基盤となる核膜孔複合体(Nuclear Pore Complex; NPC)の作動原理の解明にむけて、NPCが確立する液-液相分離(Liquid-Liquid Phase Separation; LLPS)の状態・機能相関を明らかにする。LLPSとは2つの液体が混ざり合わずに、互いに排除しあうことにより2相に分離する現象のことである。細胞核の働きについて新しい概念を創出し、広範な生命機能現象と多くの疾病症メカニズムに対する根本的な理解を目指すものである。このように、本研究課題は、新規NPC-LLPS研究領域の展開に挑戦するものである。
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| Outline of Final Research Achievements |
In this study, we successfully tracked the nanoscale dynamics of the internal structure's biofilaments in the nuclear pore complex (NPC) using HS-AFM. We discovered that in colorectal cancer cells, unlike normal cells, the thickness of individual biofilaments becomes heterogeneous, leading to increased rotation and movement of biofilaments and active formation of cancer-specific plug structures. Additionally, through gene interference experiments, we revealed that specific FG-NUPs overexpressed in colorectal cancer cells impact the dynamics of biofilaments. As a result, we achieved the first visualization of the spatiotemporal behavior of biofilaments from their formation to disappearance within the LLPS environment of the NPC.
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| Academic Significance and Societal Importance of the Research Achievements |
この研究は、数十年にわたって信じられてきた逆の結果を示し、NPC内のバイオフィラメントを追跡・操作することが可能になりました。この結果、がん細胞固有のバイオフィラメントの異常な動態と機能の相関を明らかにしました。これらの知見は、細胞内で様々な分子反応が起こるLLPS環境の物理的特性解析におけるHS-AFMの有用性を示すだけでなく、分子レベルでの核膜ダイナミクスの理解と制御に基づく新たながんの診断と治療法の開発に期待が持てます。
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Report
(3 results)
Research Products
(51 results)
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[Journal Article] Nanoscopic Assessment of Anti-SARS-CoV-2 Spike Neutralizing Antibody Using High-Speed AFM.2023
Author(s)
Keesiang Lim, Goro Nishide, Elma Sakinatus Sajidah, Tomoyoshi Yamano, Yujia Qiu, Takeshi Yoshida, Akiko Kobayashi, Masaharu Hazawa, Toshio Ando, Rikinari Hanayama, Richard W Wong
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Journal Title
Nano letters
Volume: 23
Issue: 2
Pages: 619-628
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Spatiotemporal tracking of small extracellular vesicle nanotopology in response to physicochemical stresses revealed by HS-AFM.2022
Author(s)
Elma Sakinatus Sajidah, Keesiang Lim, Tomoyoshi Yamano, Goro Nishide, Yujia Qiu, Takeshi Yoshida, Hanbo Wang, Akiko Kobayashi, Masaharu Hazawa, Firli R P Dewi, Rikinari Hanayama, Toshio Ando, Richard W Wong
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Journal Title
Journal of extracellular vesicles
Volume: 11
Issue: 11
Pages: 12275-12275
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CDK8 maintains stemness and tumorigenicity of glioma stem cells by regulating the c-MYC pathway2021
Author(s)
Fukasawa K, Kadota T, Horie T, Tokumura K, Terada R, Kitaguchi Y, Park G, Ochiai S, Iwahashi S, Okayama Y, Hiraiwa M, Yamada T, Iezaki T, Kaneda K, Yamamoto M, Kitao T, Shirahase H, Hazawa M, Wong RW, Todo T, Hirao A, Hinoi E.
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Journal Title
Oncogene
Volume: ー
Issue: 15
Pages: 2803-2815
DOI
Related Report
Peer Reviewed / Open Access
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