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2023 Fiscal Year Final Research Report

Elucidation of the transmembrane signal mechanism responsible for metabolic control by amino acid availability

Research Project

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Project/Area Number 22K19404
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 48:Biomedical structure and function and related fields
Research InstitutionOsaka University

Principal Investigator

Kanai Yoshikatsu  大阪大学, 大学院医学系研究科, 教授 (60204533)

Co-Investigator(Kenkyū-buntansha) 大垣 隆一  大阪大学, 大学院医学系研究科, 准教授 (20467525)
岡西 広樹  大阪大学, 大学院医学系研究科, 助教 (70792589)
徐 旻恵  大阪大学, 大学院医学系研究科, 助教 (20910201)
Project Period (FY) 2022-06-30 – 2024-03-31
Keywordsアミノ酸 / 輸送体 / 受容体 / シグナル情報伝達
Outline of Final Research Achievements

In order to progress protein synthesis appropriately according to the amount of nutrients supplied, it is necessary to monitor the amount of available amino acids and regulate gene expression and protein synthesis. So far, intracellular sensors have been reported that sense intracellular amino acid concentrations and transmit signals to mTORC1, which is responsible for protein synthesis regulation. In contrast, this study has demonstrated the existence of a plasma membrane-type amino acid sensor that activates mTORC1 in response to extracellular amino acids. Furthermore, we have found a specific agonist and confirmed the existence of a plasma-membrane amino acid sensor.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究は、特異的なアゴニストを見出し、細胞膜アミノ酸センサーの存在に確証を与えたものである。これまで研究されてきた細胞内アミノ酸センサーは、細胞内アミノ酸濃度を恒常的に保つフィードバック制御を担うのに対し、細胞膜センサーは、細胞外のアミノ酸濃度を感知し、アミノ酸アベイラビリティに応じてタンパク質合成を制御するフィードフォワード制御を担うものと想定される。本研究の成果は、アミノ酸シグナル研究に大きな進展をもたらし、情報受容・伝達機構の新たな領域を開拓するものと期待される。

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Published: 2025-01-30  

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