Rho family GTPases control entry of Shigella flexneri into epithelial cells but not intracellular motility.
Shigella flexneri, an invasive bacterial pathogen, promotes formation of two cytoskeletal structures: the entry focus that mediates bacterial uptake into epithelial cells and the actin-comet tail that enables the bacteria to spread intracellularly. During the entry step, secretion of bacterial invasins causes a massive burst of subcortical actin polymerization leading the formation of localised membrane projections. Fusion of these membrane ruffles leads to bacterial internalization. Inside the cytoplasm, polar expression of the IcsA protein on the bacterial surface allows polymerization of actin filaments and their organization into an actin-comet tail leading to bacterial spread. The Rho family of small GTPases plays an essential role in the organization and regulation of cellular cytoskeletal structures (i.e. filopodia, lamellipodia, adherence plaques and intercellular junctions). We show here that induction of Shigella entry foci is controlled by the Cdc42, Rac and Rho GTPases, but not by RhoG. In contrast, actin-driven intracellular motility of Shigella does not require Rho GTPases. Therefore, Shigella appears to manipulate the epithelial cell cytoskeleton both by Rho GTPase-dependent and -independent processes.
Mounier
J
J
Unité de Pathogénie Microbienne Moléculaire, INSERM U 389, Institut Pasteur, 75724 Paris Cédex 15, France.
Laurent
V
V
Hall
A
A
Fort
P
P
Carlier
M F
MF
Sansonetti
P J
PJ
Egile
C
C
D000199:Actins / Q000378:metabolism; D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000472:pathogenicity; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D009068:Movement; D009865:Oocytes / Q000382:microbiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012763:Shigella flexneri / Q000201:enzymology* / Q000472:pathogenicity* / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014981:Xenopus; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D020741:rho GTP-Binding Proteins
D000199:Actins; D001427:Bacterial Toxins; D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins; D011506:Proteins; D014157:Transcription Factors; C085379:rho GTPase-activating protein; C075397:RHOG protein, human; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D020741:rho GTP-Binding Proteins