Yersinia enterocolitica differentially modulates RhoG activity in host cells.
Pathogenic bacteria of the genus Yersinia (Y. pestis, Y. enterocolitica and Y. pseudotuberculosis) have evolved numerous virulence factors (termed a stratagem) to manipulate the activity of Rho GTPases. Here, we show that Y. enterocolitica modulates RhoG, an upstream regulator of other Rho GTPases. At the contact site of virulent Y. enterocolitica and host cells, we could visualise spatiotemporally organised activation and deactivation of RhoG. On the one hand, the beta1-integrin clustering protein Invasin on the bacterial surface was found to activate RhoG and this promoted cell invasion. On the other hand, active RhoG was downregulated by the type III secretion system effector YopE acting as a GTPase-activating protein (GAP). YopE localised to Golgi and endoplasmic reticulum, and this determined its specificity for RhoG and other selected Rho GTPases. RhoG and its downstream effector module Elmo/Dock180 controlled both Rac1 activation by Invasin and Rac1 deactivation by YopE. We propose that RhoG is a central target of the Yersinia stratagem and a major upstream regulator of Rac1 during different phases of the Yersinia infection cycle.
Roppenser
Bernhard
B
Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistrabetae 52, 20246 Hamburg, Germany.
Röder
Anja
A
Hentschke
Moritz
M
Ruckdeschel
Klaus
K
Aepfelbacher
Martin
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015008:Yersinia enterocolitica / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D003598:Cytoskeletal Proteins; C486678:ELMO2 protein, human; D011993:Recombinant Fusion Proteins; C063239:yopE protein, Yersinia; C053476:invasin, Yersinia; C075397:RHOG protein, human; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins