Novel function of organelle-specific membrane lipid environment as a platform for intracellular signal transduction

2022 Fiscal Year Final Research Report

• Project/Area Number: 17H06164
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Arai Hiroyuki 東京大学, 大学院医学系研究科(医学部), 客員研究員 (40167987)
• Co-Investigator(Kenkyū-buntansha): 河野 望 東京大学, 大学院薬学系研究科(薬学部), 准教授 (50451852) ; 向井 康治朗 東北大学, 生命科学研究科, 助教 (90767633)
• Project Period (FY): 2017-05-31 – 2022-03-31
• Keywords: 細胞内オルガネラ / 細胞情報伝達機構 / 脂質膜ドメイン

Outline of Final Research Achievements

We have discovered more than six cases in which the membrane lipids characteristic of organelles mobilize proteins involved in intracellular signal transduction and efficiently activate signal transduction on the membranes of intracellular organelles, and clarified the molecular mechanisms of these phenomena. As representative results, the Hippo-YAP signaling pathway, which is involved in cancer growth, is promoted by phosphatidylserine on the recycling endosomes, and the STING signaling pathway, which is involved in inflammation and immune signaling, is activated by sphingomyelin/cholesterol-rich membranes in the trans-Golgi network.

Free Research Field

脂質細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果として明らかとなった、細胞内シグナル統合の場としてのオルガネラ膜脂質ドメインは、細胞内オルガネラおよび生体膜脂質の機能について新しい概念を提唱するものであり、学術的意義は大きい。また本研究では、オルガネラ膜脂質ドメインの病態生理的意義にも取り組み、ATP8A1、STINGのシステイン残基、PAF-AH2など、がんや炎症性疾患に対する新たな治療標的となる分子を見出した。将来的にこれらの分子の、がんや炎症性疾患への医療応用が期待でき、社会的意義も大きい。