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The kinases Mst1 and Mst2 positively regulate phagocyte ROS induction and bactericidal activity

Mitochondria need to be juxtaposted to phagosomes to synergistically produce ample reactive oxygen species (ROS) in phagocytes for pathogens killing. However, how phagosomes transmit signal to recruit mitochondria remains unclear. Here, we report that the kinases Mst1 and Mst2 function to control RO...

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Autores principales: Geng, Jing, Sun, Xiufeng, Wang, Ping, Zhang, Shihao, Wang, Xiaozhen, Wu, Hongtan, Hong, Lixin, Xie, Changchuan, Li, Xun, Zhao, Hao, Liu, Qingxu, Jiang, Mingting, Chen, Qinghua, Zhang, Jinjia, Li, Yang, Song, Siyang, Wang, Hong-Rui, Zhou, Rongbin, Johnson, Randy L., Chien, Kun-Yi, Lin, Sheng-Cai, Han, Jiahuai, Avruch, Joseph, Chen, Lanfen, Zhou, Dawang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618176/
https://www.ncbi.nlm.nih.gov/pubmed/26414765
http://dx.doi.org/10.1038/ni.3268
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author Geng, Jing
Sun, Xiufeng
Wang, Ping
Zhang, Shihao
Wang, Xiaozhen
Wu, Hongtan
Hong, Lixin
Xie, Changchuan
Li, Xun
Zhao, Hao
Liu, Qingxu
Jiang, Mingting
Chen, Qinghua
Zhang, Jinjia
Li, Yang
Song, Siyang
Wang, Hong-Rui
Zhou, Rongbin
Johnson, Randy L.
Chien, Kun-Yi
Lin, Sheng-Cai
Han, Jiahuai
Avruch, Joseph
Chen, Lanfen
Zhou, Dawang
author_facet Geng, Jing
Sun, Xiufeng
Wang, Ping
Zhang, Shihao
Wang, Xiaozhen
Wu, Hongtan
Hong, Lixin
Xie, Changchuan
Li, Xun
Zhao, Hao
Liu, Qingxu
Jiang, Mingting
Chen, Qinghua
Zhang, Jinjia
Li, Yang
Song, Siyang
Wang, Hong-Rui
Zhou, Rongbin
Johnson, Randy L.
Chien, Kun-Yi
Lin, Sheng-Cai
Han, Jiahuai
Avruch, Joseph
Chen, Lanfen
Zhou, Dawang
author_sort Geng, Jing
collection PubMed
description Mitochondria need to be juxtaposted to phagosomes to synergistically produce ample reactive oxygen species (ROS) in phagocytes for pathogens killing. However, how phagosomes transmit signal to recruit mitochondria remains unclear. Here, we report that the kinases Mst1 and Mst2 function to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activate Rac GTPase to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for mitochondrial recruitment to phagosomes. Inactive forms of Rac, including the human Rac2(D57N) mutant, disrupt the TRAF6-ECSIT complex by sequestering TRAF6, and severely dampen ROS production and greatly increase susceptibility to bacterial infection. These findings demonstrate the TLR-Mst1-Mst2-Rac signalling axis to be critical for effective phagosome-mitochondrion function and bactericidal activity.
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spelling pubmed-46181762016-05-01 The kinases Mst1 and Mst2 positively regulate phagocyte ROS induction and bactericidal activity Geng, Jing Sun, Xiufeng Wang, Ping Zhang, Shihao Wang, Xiaozhen Wu, Hongtan Hong, Lixin Xie, Changchuan Li, Xun Zhao, Hao Liu, Qingxu Jiang, Mingting Chen, Qinghua Zhang, Jinjia Li, Yang Song, Siyang Wang, Hong-Rui Zhou, Rongbin Johnson, Randy L. Chien, Kun-Yi Lin, Sheng-Cai Han, Jiahuai Avruch, Joseph Chen, Lanfen Zhou, Dawang Nat Immunol Article Mitochondria need to be juxtaposted to phagosomes to synergistically produce ample reactive oxygen species (ROS) in phagocytes for pathogens killing. However, how phagosomes transmit signal to recruit mitochondria remains unclear. Here, we report that the kinases Mst1 and Mst2 function to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activate Rac GTPase to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for mitochondrial recruitment to phagosomes. Inactive forms of Rac, including the human Rac2(D57N) mutant, disrupt the TRAF6-ECSIT complex by sequestering TRAF6, and severely dampen ROS production and greatly increase susceptibility to bacterial infection. These findings demonstrate the TLR-Mst1-Mst2-Rac signalling axis to be critical for effective phagosome-mitochondrion function and bactericidal activity. 2015-09-28 2015-11 /pmc/articles/PMC4618176/ /pubmed/26414765 http://dx.doi.org/10.1038/ni.3268 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Geng, Jing
Sun, Xiufeng
Wang, Ping
Zhang, Shihao
Wang, Xiaozhen
Wu, Hongtan
Hong, Lixin
Xie, Changchuan
Li, Xun
Zhao, Hao
Liu, Qingxu
Jiang, Mingting
Chen, Qinghua
Zhang, Jinjia
Li, Yang
Song, Siyang
Wang, Hong-Rui
Zhou, Rongbin
Johnson, Randy L.
Chien, Kun-Yi
Lin, Sheng-Cai
Han, Jiahuai
Avruch, Joseph
Chen, Lanfen
Zhou, Dawang
The kinases Mst1 and Mst2 positively regulate phagocyte ROS induction and bactericidal activity
title The kinases Mst1 and Mst2 positively regulate phagocyte ROS induction and bactericidal activity
title_full The kinases Mst1 and Mst2 positively regulate phagocyte ROS induction and bactericidal activity
title_fullStr The kinases Mst1 and Mst2 positively regulate phagocyte ROS induction and bactericidal activity
title_full_unstemmed The kinases Mst1 and Mst2 positively regulate phagocyte ROS induction and bactericidal activity
title_short The kinases Mst1 and Mst2 positively regulate phagocyte ROS induction and bactericidal activity
title_sort kinases mst1 and mst2 positively regulate phagocyte ros induction and bactericidal activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618176/
https://www.ncbi.nlm.nih.gov/pubmed/26414765
http://dx.doi.org/10.1038/ni.3268
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