Pathogenic mechanism of neurodegenerative diseases associated with dysfunction of ubiquitin ligase

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K21706
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Institution: Hiroshima University
• Principal Investigator: Kaneko Masayuki 広島大学, 医歯薬保健学研究院(医), 准教授 (10322827)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: ユビキチンリガーゼ / 神経変性疾患 / アルツハイマー病 / ライソゾーム / オートファジー / アミノ酸トランスポーター / 神経細胞 / ユビキチン化

Outline of Final Research Achievements

We identified 37 transmembrane ubiquitin ligases. In this study, we focused on RNF182, which is upregulated in the brain of Alzheimer’s disease patients. RNF182 is expressed specifically in the central nervous system and more intensely in the hippocampus. RNF182 is mainly localized in late endosomes and lysosomes. We identified the lysosome membrane protein, LAPTM4A, as an interactor with RNF182. RNF182 processed K63-linked polyubiquitin chains on LAPTM4A and promoted interaction of LAPTM4A with amino acid transporter, LAT1. Consequently, RNF182 may induce mTOCR1 signaling that leads to inhibition of autophagy.

Free Research Field

神経化学