トップページ > セミナー開催情報 > 第7回研究所セミナー
日時
2014年3月25日(火曜日)17時~18時
場所
研究所中会議室(国府台中継)
講師
Jeffery S. Cox 先生(University of California, San Francisco)
演題
The ubiquitin ligase PARKIN is required for autophagy and host resistance to intracellular pathogens
講演要旨
Ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key immune mechanism of innate resistance to invading microbes, including the important human pathogen Mycobacterium tuberculosis. The ubiquitin ligases responsible for catalyzing ubiquitin chains that surround cytosolic intracellular bacteria are unknown. We surmised that a mechanism by which eukaryotic cells target and destroy their eubacterial-derived mitochondria (mitophagy) might be similar to the way they eliminate intracellular bacterial pathogens (xenophagy). PARKIN is a RING domain E3 ubiquitin ligase that has a well-established role in mitophagy, and null mutations in the gene encoding PARKIN (Park2) lead to autosomal recessive, juvenile Parkinson’s disease due to progressive loss of dopaminergic neuron viability. Surprisingly, mutations in the Park2 regulatory region have also been associated with increased susceptibility to intracellular bacterial pathogens in humans, including Mycobacterium leprae and Salmonella typhi, but the functional role of PARKIN in immunity has not been explored. Our work demonstrates that PARKIN plays an obligatory role in innate immune defense by marking M. tuberculosis with K63-linked ubiquitin chains. PARKIN-deficient macrophages fail to target M. tuberculosis to the autophagy pathway and to the lysosome. PARKIN-deficient mice are exquisitely sensitive to M. tuberculosis infection, and fail to control infection by Listeria monocytogenes, another intracellular pathogen. PARKIN appears to play a conserved role in metazoan innate defense, as PARKIN-deficient flies are also susceptible to microbial infections. Thus, PARKIN regulates both neuronal disease due to its role in mitophagy, and resistance to pathogens via its unexpected role in xenophagy.
(NIH P01 AI063302)
研究所セミナー:開催スケジュール
- 第13回 田中 啓二 先生(東京都医学総合研究所)
(12月8日) - 第12回 綿田 裕孝 先生(順天堂大学) (10月20日)
- 第11回 須田 年生 先生(慶応大学) (9月29日)
- 第10回 北 潔 先生(東京大学) (7月14日)
- 第9回 徳永 勝士 先生(東京大学) (6月9日)
- 第8回 小安 重夫 先生(理化学研究所) (4月21日)
- 第7回 Jeffery S. Cox 先生 (UCSF) (3月25日)
- 第6回 中釜 斉 先生(国立がんセンター) (1月21日)
主催・連絡先
国立国際医療研究センター研究所長:清水 孝雄