Mechanism of regulation of liquid-liquid phase separation by importin-beta

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16060
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Ritsumeikan University
• Principal Investigator: Yoshizawa Takuya 立命館大学, 生命科学部, 講師 (50779056)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 液－液相分離 / 核内輸送受容体 / RNA結合タンパク質 / 筋萎縮性側索硬化症

Outline of Final Research Achievements

Nuclear import receptors, karyopherin-βs inhibit liquid-liquid phase separation (LLPS) of client proteins. Dysregulation of LLPS leads to an aggregation of the client proteins, eventually causing fatal neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). We studied dysregulation by mutations of the client protein or repeat peptide inhibitor bound to karyopherin-βs. In addition, we developed a new technique to track forming or vanishing droplets by LLPS.

Free Research Field

相分離生物学

Academic Significance and Societal Importance of the Research Achievements

液－液相分離を調節するタンパク質の解析は未だ事例が少なく、新たなシャペロンのカテゴリーとして開拓されつつある領域であり、そのメカニズムに迫った（学術的意義）。また、液－液相分離相分離の状態は解析が困難であり、新規な解析法を開発した（学術的意義）。タンパク質の凝集は重篤な疾患とも密接に関わり、疾患関連変異体や関連遺伝子産物を用いた本研究は、病態の発症メカニズムに迫るものである（社会的意義）。