Genetic and biochemical analysis of the ER quality control of membrane proteins

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K19306
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Nagoya City University
• Principal Investigator: Nakatsukasa Kunio 名古屋市立大学, 大学院理学研究科, 准教授 (90547522)
• Project Period (FY): 2018-06-29 – 2022-03-31
• Keywords: 小胞体 / 膜タンパク質 / ユビキチン / プロテアソーム / 分解

Outline of Final Research Achievements

Misfolded or unassembled proteins in the endoplasmic reticulum (ER) are degraded by the proteasome. This process is referred to as ER-associated degradation or ERAD. In this study, we analyzed the mechanisms of membrane protein degradation during ERAD: (1)Experimental and theoretical analysis to predict membrane protein insertion in yeast cells; (2)Physiological role of the ERAD of membrane proteins; (3)Genetic analysis of the retrotranslocation complex. (4)We also performed collaborative research to study ERAD in mammals.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

細胞には立体構造の形成に失敗した異常タンパク質を特異的に認識して分解する品質管理の仕組みが備わっている。本研究では、小胞体の膜に存在する異常タンパク質に着目し、出芽酵母の遺伝学、生化学の手法を駆使して、分解の仕組みを詳細に解析した。本研究で得られた成果は、異常タンパク質の蓄積を防ぐ方法論の開発につながるものと期待される。