Study on molecular mechanisms of fluidity of the endoplasmic reticulum

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06836
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Kobe University
• Principal Investigator: Sakisaka Toshiaki 神戸大学, 医学研究科, 教授 (80359843)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 細胞小器官 / 小胞体 / 膜変形タンパク質

Outline of Final Research Achievements

Endoplasmic reticulum (ER) is the continuous membrane system composed of tubules and sheets in the cytoplasm. The ER tubules are interconnected by three-way junctions, resulting in formation of the reticular ER network. The ER structure is not static, but undergoes constant remodeling, such as a tubule to sheet conversion, through dynamic regulation of the three-way junctions. While the N-terminal ubiquitin ligase activity of lunapark regulates the reticular ER network formation through stabilizing the three-way junctions, the molecular mechanism of how the ubiquitin ligase activity is regulated remains unknown. In this study, we identified p63 as a novel substrate for ubiquitination by lunapark. Moreover, we revealed that p60, a protein that bound to lunapark, regulated the ubiquitin ligase activity of lunapark.

Free Research Field

医化学一般

Academic Significance and Societal Importance of the Research Achievements

本研究のlunaparkによるユビキチン化タンパク質p63の発見、さらにはlunaparkのユビキチンリガーゼ活性制御タンパク質p60の発見、これら２つのタンパク質がthree-way junctionの動態制御を介して小胞体流動に寄与していることを提示したものであり、学術的な意義が大きいと考えている。小胞体流動の破綻は遺伝性痙性対麻痺などの神経変性疾患を引き起こすことから、本研究の成果が神経変性疾患の発症機序の理解や治療薬の開発に繋がる可能性が考えられ、社会的にも意義が大きいと考えている。