Molecular mechanism underlying STING activation/inactivation with membrane traffic

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H00974
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Tohoku University
• Principal Investigator: TAGUCHI TOMOHIKO 東北大学, 生命科学研究科, 教授 (10300881)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: membrane traffic / innate immunity / microautophagy / Golgi / lysosome

Outline of Final Research Achievements

This study showed that activation and inactivation of STING was strictly regulated by membrane traffic, i.e., ER-the Golgi-recycling endosomes-lysosome. The retrograde transport from the Golgi to the ER was found to be essential for the steady state localization of STING at the ER. The impaired retrograde traffic resulted in the spontaneous activation of STING at the Golgi, which underlies the pathogenesis of the COPA syndrome. The delivery and degradation of STING at lysosomes was found to be mediated by microautophagy, in which lysosomes directly encapsulate STING into lysosomal lumen.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

リソソームが、細胞質（膜）成分を直接飲み込み分解する能力（ミクロオートファジー）を有していることを示した本研究成果は、リソソームの新しい機能を明らかにしたという学術的価値をもつ。今後は、隔離膜を利用するマクロオートファジーとどのように使い分けがなされているのか追究していくことで、細胞内分子のホメオスタシス制御について新しい概念が生まれることが期待される。