title: Yersinia outer protein YopE affects the actin cytoskeleton in Dictyostelium discoideum through targeting of multiple Rho family GTPases.
abstract: BACKGROUND
  All human pathogenic Yersinia species share a virulence-associated type III secretion system that translocates Yersinia effector proteins into host cells to counteract infection-induced signaling responses and prevent phagocytosis. Dictyostelium discoideum has been recently used to study the effects of bacterial virulence factors produced by internalized pathogens. In this study we explored the potential of Dictyostelium as model organism for analyzing the effects of ectopically expressed Yersinia outer proteins (Yops).
  
  
  RESULTS
  The Yersinia pseudotuberculosis virulence factors YopE, YopH, YopM and YopJ were expressed de novo within Dictyostelium and their effects on growth in axenic medium and on bacterial lawns were analyzed. No severe effect was observed for YopH, YopJ and YopM, but expression of YopE, which is a GTPase activating protein for Rho GTPases, was found to be highly detrimental. GFP-tagged YopE expressing cells had less conspicuous cortical actin accumulation and decreased amounts of F-actin. The actin polymerization response upon cAMP stimulation was impaired, although chemotaxis was unaffected. YopE also caused reduced uptake of yeast particles. These alterations are probably due to impaired Rac1 activation. We also found that YopE predominantly associates with intracellular membranes including the Golgi apparatus and inhibits the function of moderately overexpressed RacH.
  
  
  CONCLUSIONS
  The phenotype elicited by YopE in Dictyostelium can be explained, at least in part, by inactivation of one or more Rho family GTPases. It further demonstrates that the social amoeba Dictyostelium discoideum can be used as an efficient and easy-to-handle model organism in order to analyze the function of a translocated GAP protein of a human pathogen.
authors: Zentrum für Biochemie und Zentrum für Molekulare Medizin, Medizinische Fakultät, Universität Köln, Joseph-Stelzmann-Strasse 52, 50931 Köln, Germany. gvlahou@uni-koeln.de
authors: Georgia
authors: G
authors: Vlahou
authors: Oxana
authors: O
authors: Schmidt
authors: Bettina
authors: B
authors: Wagner
authors: Handan
authors: H
authors: Uenlue
authors: Petra
authors: P
authors: Dersch
authors: Francisco
authors: F
authors: Rivero
authors: Barbara A
authors: BA
authors: Weissenmayer
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D004023:Dictyostelium / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D010587:Phagocytosis; D014170:Transformation, Genetic; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism; D015011:Yersinia pseudotuberculosis / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D001425:Bacterial Outer Membrane Proteins; D037521:Virulence Factors; C063239:yopE protein, Yersinia; D020741:rho GTP-Binding Proteins