Removal Mechanism of Nuclear Aggregates - Are nuclear aggregates transported out of the nucleus by the same mechanism as viruses?

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K06569
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Shinkai Yoichi 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ長 (00758378)
• Co-Investigator(Kenkyū-buntansha): 戸井 基道 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ付 (50344213)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 線虫C. elegans / 神経変性疾患 / 液-液相分離 / FGリピートタンパク質

Outline of Final Research Achievements

Cells maintain their cellular functions by removing unnecessary protein aggregates. We found that the nuclear membrane was greatly deformed and the protein aggregates were ejected from the nucleus, when protein aggregates were accumulated in the nucleus of C. elegans neurons. Using proximity-dependent labeling, we comprehensively identified a group of molecules that interact with nuclear aggregates and found FG repeat proteins that closely resemble the constituent molecules of the nuclear membrane pore complexes. The liquid-liquid phase separation role of FG repeat protein is known as a selective barrier for nuclear transport, but its other functions were not known. The function of FG repeat protein in the removal process of protein aggregates was clarified by our study.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

神経変性疾患の原因メカニズムの一つとして液-液相分離の破綻が注目されている。本研究では、FGリピートタンパク質の液-液相分離の細胞機能やその破綻の影響を明らかにしてきた。今後、本研究がさらに進展することによって、神経変性疾患の発症メカニズムやバイオミメティクスによる治療法の発見などが期待できる。