2018 Fiscal Year Final Research Report
Regulation of xenophagy aginst Group A Streptococcus
| Project/Area Number |
16H05188
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including mycology)
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
野澤 孝志 京都大学, 医学研究科, 助教 (10598858)
相川 知宏 京都大学, 医学研究科, 助教 (70725499)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | A群レンサ球菌 / オートファジー / Rab35 / TDC1D10A / ゼノファジー |
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| Outline of Final Research Achievements |
Autophagy targets intracellular molecules, damaged organelles, and invading pathogens for degradation in lysosomes. Recent studies have identified autophagy receptors that facilitate this process by binding to ubiquitinated targets, including NDP52. Here, we demonstrate that the small guanosine triphosphatase Rab35 directs NDP52 to the corresponding targets of multiple forms of autophagy. The active GTP-bound form of Rab35 accumulates on bacteria-containing endosomes, and Rab35 directly binds and recruits NDP52 to internalized bacteria. Additionally, Rab35 promotes interaction of NDP52 with ubiquitin. This process is inhibited by TBC1D10A, a GAP protein that inactivates Rab35, but stimulated by autophagic activation via TBK1 kinase, which associates with NDP52. Rab35, TBC1D10A and TBK1 regulate NDP52 recruitment to damaged mitochondria and to autophagosomes to promote mitophagy and maturation of autophagosomes, respectively.
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| Free Research Field |
細菌学
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| Academic Significance and Societal Importance of the Research Achievements |
細菌感染によるオートファジーの誘導機構については、これまでに様々な菌を対象として多種多様な説が提唱されているが、「どのように菌を見分けて、オートファジーを誘導しているのか」という点については明らかとされていない。本研究の結果はオートファゴソーム形成の初期プロセスである隔離膜形成の誘導に必須な細菌菌体に存在する糖鎖を認識するユビキチンシステムを同定することで、新たな自然免疫系の一端を明らかとするという新規の展開が期待できると考えている．
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