A bacterial effector targets host DH-PH domain RhoGEFs and antagonizes   macrophage phagocytosis

doi:10.1038/emboj.2010.33

CORC > 北京大学 > 生命科学学院

	A bacterial effector targets host DH-PH domain RhoGEFs and antagonizes macrophage phagocytosis
	Dong, Na ; Liu, Liping ; Shao, Feng
刊名	embo journal
	2010
关键词	pathogen-host interaction Rho GTPases signal transduction type III effectors ENTEROPATHOGENIC ESCHERICHIA-COLI NUCLEOTIDE EXCHANGE FACTOR III EFFECTOR ACTIN-CYTOSKELETON PROTEIN-KINASE P115 RHOGEF FAMILY IDENTIFICATION ACTIVATION RHOA
DOI	10.1038/emboj.2010.33
英文摘要	Bacterial pathogens often harbour a type III secretion system (TTSS) that injects effector proteins into eukaryotic cells to manipulate host processes and cause diseases. Identification of host targets of bacterial effectors and revealing their mechanism of actions are crucial for understating bacterial virulence. We show that EspH, a type III effector conserved in enteric bacterial pathogens including enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli and Citrobacter rodentium, markedly disrupts actin cytoskeleton structure and induces cell rounding up when ectopically expressed or delivered into HeLa cells by the bacterial TTSS. EspH inactivates host Rho GTPase signalling pathway at the level of RhoGEF. EspH directly binds the DH-PH domain in multiple RhoGEFs, which prevents their binding to Rho and thereby inhibits nucleotide exchange-mediated Rho activation. Consistently, infection of mouse macrophages with EPEC harbouring EspH attenuates phagocytosis of the bacteria as well as Fc gamma R-mediated phagocytosis. EspH represents the first example of targeting RhoGEFs by bacterial effectors, and our results also reveal an unprecedented mechanism used by enteric pathogens to counteract the host defence system. The EMBO Journal (2010) 29, 1363-1376. doi: 10.1038/emboj.2010.33; Published online 18 March 2010; Biochemistry & Molecular Biology; Cell Biology; SCI(E); PubMed; 31; ARTICLE; 8; 1363-1376; 29
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/319976]
专题	生命科学学院
推荐引用方式 GB/T 7714	Dong, Na,Liu, Liping,Shao, Feng. A bacterial effector targets host DH-PH domain RhoGEFs and antagonizes macrophage phagocytosis[J]. embo journal,2010.
APA	Dong, Na,Liu, Liping,&Shao, Feng.(2010).A bacterial effector targets host DH-PH domain RhoGEFs and antagonizes macrophage phagocytosis.embo journal.
MLA	Dong, Na,et al."A bacterial effector targets host DH-PH domain RhoGEFs and antagonizes macrophage phagocytosis".embo journal (2010).