RRC ID 1102
Author Matsuzawa T, Kuwae A, Yoshida S, Sasakawa C, Abe A.
Title Enteropathogenic Escherichia coli activates the RhoA signaling pathway via the stimulation of GEF-H1.
Journal EMBO J
Abstract 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.
Volume 23(17)
Pages 3570-82
Published 2004-9-1
DOI 10.1038/sj.emboj.7600359
PII 7600359
PMID 15318166
PMC PMC516631
MeSH Actins / metabolism Animals Cytoskeleton / metabolism Cytosol / metabolism Escherichia coli / pathogenicity* Escherichia coli / physiology Escherichia coli Proteins / physiology Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism* Mice Microtubules / metabolism Models, Biological Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism* Rho Guanine Nucleotide Exchange Factors Signal Transduction Swiss 3T3 Cells Tubulin / metabolism rhoA GTP-Binding Protein / metabolism*
IF 11.227
Times Cited 116
Pathogenic microorganisms ?