Role of Ribosome-associated quality control in mammalian neurons

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07243
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Tohoku University
• Principal Investigator: Udagawa Tsuyoshi 東北大学, 薬学研究科, 助教 (20644199)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 翻訳 / 品質管理 / 脳機能制御

Outline of Final Research Achievements

In order to elucidate physiological function of ribosome-associated quality control (RQC), a quality control for aberrant protein synthesis, in neurons, we have performed a series of behavioral assays and neuron morphogenesis and survival analysis. we found that clearance of the proteins with CAT-tail which is a peptide tag attached to C-terminal end of nascent peptides during RQC and promote efficient degradation of nascent peptides is crucial for the maintenance of morphology of young developing neurons. CAT-tailed products are likely prone to aggregate and eventually induce cell death. On the other hands, knockdown of RQT (RQC trigger) factors in the mouse hippocampus affected anxiety and long-term memory formation.

Free Research Field

分子医化学

Academic Significance and Societal Importance of the Research Achievements

翻訳の異常に起因する新生タンパク質の品質管理機構であるribosome-associated quality control (RQC)は、近年、その分子機構が出芽酵母において詳細に解析が進められているが、哺乳類細胞や個体レベルでの重要性はまだほとんど明らかにされていない。本研究ではRQC因子の脳神経系における昨日解析を行い、神経突起の形態形成や神経細胞生存、また、個体レベルでは、学習と記憶、不安などの高次脳機能にRQC因子が重要な役割を果たすことが明らかにされた。