Enteropathogenic Escherichia coli activates the RhoA signaling pathway via the stimulation of GEF-H1.
Enteropathogenic Escherichia coli delivers a subset of effectors into host cells via a type III secretion system, and this step is required for the progression of disease. Here, we show that the type III effectors, EspG and its homolog Orf3, trigger actin stress fiber formation and the destruction of the microtubule networks beneath adherent bacteria. Both effectors were shown to possess the ability to interact with tubulins, and to stimulate microtubule destabilization in vitro. A recent study showed that microtubule-bound GEF-H1, a RhoA-specific guanine nucleotide exchange factor, was converted to its active form by microtubule destabilization, and this sequence of events resulted in RhoA stimulation. Indeed, EspG- and Orf3-induced stress fiber formation was inhibited by the expression of dominant-negative forms of GEF-H1 and RhoA, but not of Rac1 and Cdc42, and by treatment with a ROCK inhibitor. These results indicate that the impact of EspG/Orf3 on microtubule networks triggers the activation of the RhoA-ROCK signaling pathway via GEF-H1 activity. This report reveals for the first time that a pathogen can exploit the host factor GEF-H1.
Department of Infection Control and Immunology, Laboratory of Bacterial Infection, Kitasato Institute for Life Sciences, Kitasato University, Shirokane, Minato-ku, Tokyo, Japan.
Takeshi
T
Matsuzawa
Asaomi
A
Kuwae
Sei
S
Yoshida
Chihiro
C
Sasakawa
Akio
A
Abe
D000199:Actins / Q000378:metabolism; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004926:Escherichia coli / Q000472:pathogenicity* / Q000502:physiology; D029968:Escherichia coli Proteins / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction; D041701:Swiss 3T3 Cells; D014404:Tubulin / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; C577402:Arhgef2 protein, mouse; D029968:Escherichia coli Proteins; C429282:EspG protein, E coli; D020662:Guanine Nucleotide Exchange Factors; D011518:Proto-Oncogene Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; D014404:Tubulin; D020742:rhoA GTP-Binding Protein