2022 Fiscal Year Final Research Report
Functional Dynamics of Liquid-Liquid Phase Separation Mediated by Nuclear Pore Complex
Project/Area Number |
21K19043
|
Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 37:Biomolecular chemistry and related fields
|
Research Institution | Kanazawa University |
Principal Investigator |
Wong Richard 金沢大学, ナノ生命科学研究所, 教授 (30464035)
|
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)
|
Project Period (FY) |
2021-07-09 – 2023-03-31
|
Keywords | 核膜孔複合体 |
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.
|
Free Research Field |
生体分子化学およびその関連分野
|
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。
|