Molecular understanding of osmotic stress sensing and response

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H03995
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: ICHIJO HIDENORI 東京大学, 大学院薬学系研究科(薬学部), 教授 (00242206)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ASK3 / 浸透圧ストレス受容 / 浸透圧ストレス応答 / 細胞体積制御 / VRAC/LRRC8 / アポトーシス / 液―液相分離 / ポリADPリボース

Outline of Final Research Achievements

Cells are constantly exposed to osmotic stress that forces them to change their volume due to osmotic pressure differences between the inside and outside of the cell, so called osmotic stress, and they maintain a constant volume by sensing osmotic pressure changes and responding appropriately. Until now, most studies have been based on the idea that osmotic changes without physical substance are sensed through changes in the cell membrane, which is in contact with the extracellular environment.
Using the ASK3 protein as a research model, we have elucidated that cells sense osmotic stress internally using the physical phenomenon of liquid-liquid phase separation as a "trigger". These are the results of taking advantage of molecular biological and biochemical methods and computer simulations.

Free Research Field

生化学、分子生物学、特に細胞のストレス応答の分子メカニズムとその解明に立脚した創薬基盤形成

Academic Significance and Societal Importance of the Research Achievements

本研究はいわゆる基礎研究に相当しますが、本研究成果によってASK3の役割から期待される高血圧疾患や浮腫などに対する新規治療薬の開発に向けて前進しました。さらに本研究成果によって得られた知見を活かして液―液相分離を積極的に操作することで、神経変性疾患など多くの疾患に対する新規治療戦略の開発に発展することも期待されます。