The cytotoxin YopT of Yersinia enterocolitica induces modification and cellular redistribution of the small GTP-binding protein RhoA.
Pathogenic Yersinia enterocolitica produces two virulence plasmid-encoded cytotoxins, YopE and YopT, that are translocated into target cells where they disrupt the actin cytoskeleton. Here we show that infection of cells with wild type Y. enterocolitica and a yopE mutant, but not with a yopT mutant, induces an increase in the electrophoretic mobility of the small GTPase RhoA. As tested by isoelectric focusing, YopT-dependent modification resulted in an acidic shift of RhoA. Furthermore, RhoA modification induced by YopT was accompanied by redistribution of membrane-bound RhoA toward the cytosol. Finally, a yopE mutant of Y. enterocolitica expressing the cytotoxic activity of YopT specifically disrupted RhoA-controlled actin stress fibers. These findings provide evidence for inactivation of RhoA by the translocated Y. enterocolitica cytotoxin YopT and suggest a novel inhibitory modification of RhoA by a bacterial virulence factor.
Zumbihl
R
R
Max von Pettenkofer Institut für Hygiene und Mikrobiologie, Pettenkoferstrasse 9a, 80336 Munich, Germany.
Aepfelbacher
M
M
Andor
A
A
Jacobi
C A
CA
Ruckdeschel
K
K
Rouot
B
B
Heesemann
J
J
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology*; D019556:COS Cells; D003546:Cysteine Endopeptidases; D003603:Cytotoxins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000382:microbiology; D007525:Isoelectric Focusing; D008856:Microscopy, Fluorescence; D009154:Mutation; D014774:Virulence; D015008:Yersinia enterocolitica / Q000737:chemistry* / Q000472:pathogenicity; D020742:rhoA GTP-Binding Protein / Q000737:chemistry*
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D003603:Cytotoxins; C116117:YopT protein, Yersinia; C063239:yopE protein, Yersinia; D003546:Cysteine Endopeptidases; D020742:rhoA GTP-Binding Protein