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	Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity
	Jing Geng ; Geng J(耿晶) ; Xiufeng Sun ; Sun XF(孙秀峰) ; Ping Wang ; Shihao Zhang ; Zhang SH(张世浩) ; Xiaozhen Wan ; Wang XZ(王晓珍) ; Hongtan Wu ; Lixin Hong ; Changchuan Xie ; Xun Li ; Hao Zhao ; Qingxu Liu ; Mingting Jiang ; Qinghua Chen ; Jinjia Zhang ; Yang Li ; Siyang Song ; Hong-Rui Wang ; Rongbin Zhou ; Randy L Johnson ; Kun-Yi Chien ; Sheng-Cai Li ; Jiahuai Han ; Joseph Avruch ; Lanfen Chen ; Chen LF(陈兰芬) ; Dawang Zhou ; Zhou DW(周大旺)
	2015-09-28
英文摘要	该研究成果揭示了吞噬性细胞内Hippo信号通路关键激酶Mst1和Mst2通过活化Rac家族蛋白来调节线粒体向吞噬小泡募集并释放ROS来清除病原体，这个生物学过程在天然免疫和宿主防御中发挥着重要作用。该成果解析了人的Mst1基因缺失或Rac2基因突变引发免疫缺陷综合症的致病机理，为研究人类感染性疾病提供了全新的视角。 该论文的主要工作由2012级博士生耿晶、2013级博士生孙秀峰以及王平、张世浩和王晓珍等学生共同承担，并与厦门市第一医院、台湾长庚大学、中国科学技术大学等单位合作完成，通讯作者为周大旺教授和陈兰芬教授。该研究工作获得了“青年千人计划”、国家自然科学基金委和科技部的资助。; Mitochondria need to be juxtaposed to phagosomes for the synergistic production of ample reactive oxygen species (ROS) in phagocytes to kill pathogens. However, how phagosomes transmit signals to recruit mitochondria has remained unclear. Here we found that the kinases Mst1 and Mst2 functioned to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activated the GTPase Rac to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for the recruitment of mitochondria to phagosomes. Inactive forms of Rac, including the human Rac2D57N mutant, disrupted the TRAF6-ECSIT complex by sequestering TRAF6 and substantially diminished ROS production and enhanced susceptibility to bacterial infection. Our findings demonstrate that the TLR-Mst1-Mst2-Rac signaling axis is critical for effective phagosome-mitochondrion function and bactericidal activity.; Supported by the National Basic Research Program (973) of China (2015CB910502 to L.C.), China's 1000 Young Talents Program (D.Z. and L.C.), the 111 Projects (B12001 and B06016), the Fundamental Research Funds for the Central Universities of China-Xiamen University (CXB2014004 to J.Z.; 20720140551 to L.C.; and 2013121034 and 20720140537 to D.Z.), the National Natural Science Foundation of China (31270918, 81222030 and J1310027 to D.Z.; 81372617, 81422018 and U1405225 to L.C.; 81472229 to L.H.; and 81302529 to X.L.), the Natural Science Foundation of Fujian (2013J06011 to D.Z. and 2014D007 to X.L.), the US National Institutes of Health (RO1 CA136567 for J.A.) and institutional funds from Massachusetts General Hospital (for J.A.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
语种	英语
出版者	nature publishing group
内容类型	期刊论文
源URL	[http://dx.doi.org/10.1038/ni.3268]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Jing Geng,Geng J,Xiufeng Sun,et al. Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity[J],2015.
APA	Jing Geng.,耿晶.,Xiufeng Sun.,孙秀峰.,Ping Wang.,...&周大旺.(2015).Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity..
MLA	Jing Geng,et al."Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity".(2015).

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