Functional analysis of Legionella effector protein manipulating COPI vesicles
| Project/Area Number |
18K15145
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49050:Bacteriology-related
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| Research Institution | Gifu University |
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Principal Investigator |
Kitao Tomoe 岐阜大学, 大学院医学系研究科, 助教 (80462787)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 細菌感染 / 細胞内寄生 / エフェクター / 脱ユビキチン化酵素 / SNARE / 小胞輸送 / レジオネラ / ユビキチン / 脱ユビキチン化 / v-SNARE / 病原性 / 病原細菌 / 膜輸送 |
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| Outline of Final Research Achievements |
The intracellular bacterial pathogen L. pneumophila uses many effector proteins delivered by the type IV secretion system to hijack the early secretory pathway to establish its replicative niche, known as the Legionella-containing vacuole (LCV). On LCV biogenesis, the endoplasmic reticulum derived v-SNARE Sec22b is recruited to the bacterial phagosome and forms non-canonical pairings with t-SNAREs from the plasma membrane. In this study we identified a Legionella deubiquitinase (DUB) LotB that could modulate the early secretory pathway by interacting with host COPI vesicles when ectopically expressed. Also we found that the Sec22b was ubiquitinated upon L. pneumophila infection, subsequently, LotB deconjugated K63-linked ubiquitins from Sec22b. The DUB activity of LotB stimulated dissociation of the t-SNARE syntaxin 3 from Sec22b, which resides on the LCV. Our study highlights a bacterial strategy manipulating the dynamics of infection-induced SNARE pairing using a bacterial DUB.
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| Academic Significance and Societal Importance of the Research Achievements |
レジオネラ感染において重要な役割を担うエフェクタータンパク質の機能を解明すること、ならびに、エフェクタータンパク質を宿主に輸送するIV型分泌装置の機能を解明することは、レジオネラ感染を制御しうる新たな治療法開発に役立つ。本研究課題では、機能未知レジオネラエフェクタータンパク質Lpg1621の機能解析を通してレジオネラ感染におけるLCV構築メカニズムの一端を解明することができた。
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Report
(4 results)
Research Products
(17 results)
