2022 Fiscal Year Final Research Report

Exploration of ER-phagy substrates involved in brain aging and its application to the control of neuronal senescence

Research Project

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Project/Area Number	20K21751
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research Institution	Gifu University
Principal Investigator	Oh-hashi Kentaro 岐阜大学, 工学部, 准教授 (50332953)
Co-Investigator(Kenkyū-buntansha)	石垣診祐名古屋大学, 医学系研究科, 特任准教授 (40378170) 天谷文昌京都府立医科大学, 医学(系)研究科(研究院), 教授 (60347466) 内尾こずえ国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所難治性疾患研究開発・支援センター, 主任研究員 (70373397)
Project Period (FY)	2020-07-30 – 2023-03-31
Keywords	ER-phagy / ER stress / ERAD / Golgi stress / FAM134B
Outline of Final Research Achievements	In this study, we investigated ER-autophagy (ER-phagy), one of the ER regulatory mechanisms. In particular, we focused on FAM134B, one of the ER-phagy receptors, which is involved in hereditary sensory nerve abnormalities. First, we analyzed endogenous FAM134B protein expression under various nutritional deficiency conditions and found that the protein was significantly decreased by serum and amino acid deprivation. Next, we established FAM134B-deficient Neuro2a cells by genome editing technology, and transfected wild-type and HSAN2B-linked FAM134B into the cells and characterized their features. These findings are expected to lead to the development of new drugs targeting the ER.
Free Research Field	細胞分子生物学、健康科学
Academic Significance and Societal Importance of the Research Achievements	本研究では、ER-phagy受容体の１つFAM134Bタンパク質の発現制御および変異FAM134BがER-phagyに及ぼす影響について検討を行った。とりわけ、本研究において樹立したFAM134B欠損細胞株をはじめとする小胞体制御因子欠損細胞株や生細胞にてER-phagy解析が検討可能なNanoBiT reporterシステムは、今後の詳細な解析や薬剤開発に役立つものと考えられる。