| Project/Area Number |
18K07109
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49050:Bacteriology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
相川 知宏 京都大学, 医学研究科, 助教 (70725499)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | オートファジー / A群レンサ球菌 / 糖鎖 / ゼノファジー / ガレクチン / GBP1 / TBK1 / TBC1D9 / FBXO2 / 糖鎖認識 |
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| Outline of Final Research Achievements |
Autophagy degrades invading bacterial pathogens such as group A Streptococcus (GAS) to defend cells. Although invading bacteria are known to be marked with ubiquitin and selectively targeted by autophagy, how ubiquitin ligases recognize invading bacteria is poorly understood. In this study, we show that FBXO2, a glycoprotein-specific receptor for substrate in the SCF (SKP1/CUL1/F-box protein) ubiquitin ligase complex, mediates the recognition of GlcNAc side chains of the GAS surface carbohydrate and promotes ubiquitin-mediated autophagy. FBXO2 targets cytosolic GAS through its sugar-binding motif and GlcNAc expression on the GAS surface. FBXO2 knockout resulted in a decrease in ubiquitin accumulation on intracellular GAS and degradation of bacteria. Furthermore, SCF components are also required for ubiquitin-mediated autophagy against GAS. Thus, we propose that SCF-FBXO2 recognizes GlcNAc residues of GAS surface carbohydrates and functions in ubiquitination during autophagy.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、ヒト細胞内に侵入した病原菌の糖鎖成分がヒトの受容体によって認識されることで菌がユビキチン化修飾され、免疫経路の一つであるオートファジーが誘導されることが明らかになりました。これは、新たなユビキチン化機構の可能性を示唆しており、生物学的意義の高い知見であると考えられます。今後この認識機構の詳細を明らかにするとともに、この認識メカニズム標的とした創薬につなげることで、新たな感染症制御法の開発に貢献できる可能性があります。
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