A novel regulation of the endoplasmic reticulum morphology by ubiquitination

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06220
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Kobe University
• Principal Investigator: Hiroaki Kajiho 神戸大学, 医学研究科, 講師 (70401221)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 小胞体 / ユビキチンリガーゼ

Outline of Final Research Achievements

The endoplasmic reticulum (ER) tubules connect each other by three-way junctions, resulting in formation of the network. The tubular ER network is shaped by the ER membrane-shaping proteins. The tubular ER network undergoes constant remodeling, especially during cell division or under stressed conditions. During remodeling of the tubular ER network, the ER membrane-shaping proteins have to be degraded. However, the molecular mechanism of the degradation of the ER membrane-shaping proteins remains unknown. We found that lunapark, a ubiquitin ligase localizing at three-way junctions of the tubular ER network, ubiquitinates p66, one of the ER membrane-shaping proteins involved in connecting the ER tubules. Our studies implicate that lunapark and p66 play important roles in generating and stabilizing the three-way junctions for the proper tubular ER network formation.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

小胞体でのユビキチン化反応は一般的にはタンパク質の品質管理機構として用いられる。本研究課題により、lunaparkによるユビキチン化反応が小胞体の形状変化に重要であることが明らかとなり、小胞体でのユビキチン化反応が新たな役割を持つことを提唱できた。
筋萎縮性側索硬化症やアルツハイマー病などの神経変性疾患の際には小胞体のチューブ構造を支えるタンパク質の量が変わり、小胞体の形状が異常になることが報告されている。本研究課題により、lunaparkの機能異常が神経変性疾患の発症に関わる可能性が考えられる。今後、lunaparkをターゲットとした神経変性疾患に対する創薬への応用が十分考えられる。