A salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion.
An essential feature of the bacterial pathogen Salmonella spp. is its ability to enter cells that are normally non-phagocytic, such as those of the intestinal epithelium. The bacterium achieves entry by delivering effector proteins into the host-cell cytosol by means of a specialized protein-secretion system (termed type III), which causes reorganization of the cell's actin cytoskeleton and ruffling of its membrane. One of the bacterial effectors that stimulates these cellular responses is SopE, which acts as a guanyl-nucleotide-exchange factor on Rho GTPase proteins such as Cdc42 and Rac. As the actin-cytoskeleton reorganization induced by Salmonella is reversible and short-lived, infected cells regain their normal architecture after bacterial internalization. We show here that the S. Typhimurium effector protein SptP, which is delivered to the host-cell cytosol by the type-III secretion system, is directly responsible for the reversal of the actin cytoskeletal changes induced by the bacterium. SptP exerts this function by acting as a GTPase-activating protein (GAP) for Rac-1 and Cdc42.
Fu
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Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale School of Medicine, New Haven, Connecticut 06536, USA.
Galán
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JE
D000199:Actins / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D001422:Bacterial Adhesion / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000382:microbiology; D004926:Escherichia coli; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D009154:Mutation; D011494:Protein Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
D000199:Actins; D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D001120:Arginine; D011494:Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D017027:Protein Tyrosine Phosphatases; C439890:sptP protein, Salmonella typhimurium; D019204:GTP-Binding Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae