Ruffles induced by Salmonella and other stimuli direct macropinocytosis of bacteria

Francis, Carol L.; Ryan, Timothy A.; Jones, Bradley D.; Smith, Stephen J.; Falkow, Stanley

doi:10.1038/364639a0

Cited by 413 publications

(324 citation statements)

References 28 publications

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“…5, A and B). At this time point extensive membrane ruffling, characteristic of Salmonella invasion, is evident where the bacteria are in contact with the host cell (29). Bacterial-induced translocation of Akt is still evident 30 min post-infection, which is similar to the localization pattern induced by cell-cell or cellmatrix contact in epithelial cells (22).…”

Section: Pi3-k Activation and Rapid Translocation Of Akt To The Plasmsupporting

confidence: 54%

Activation of Akt/Protein Kinase B in Epithelial Cells by theSalmonella typhimurium Effector SigD

Steele‐Mortimer

Knodler

Marcus

et al. 2000

Journal of Biological Chemistry

179

244

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The serine-threonine kinase Akt is a protooncogene involved in the regulation of cell proliferation and survival. Activation of Akt is initiated by binding to the phospholipid products of phosphoinositide 3-kinase at the inner leaflet of the plasma membranes followed by phosphorylation at Ser 473 and Thr 308 . We have found that Akt is activated by Salmonella enterica serovar Typhimurium in epithelial cells. A bacterial effector protein, SigD, which is translocated into host cells via the specialized type III secretion system, is essential for Akt activation. In HeLa cells, wild type S. typhimurium induced translocation of Akt to membrane ruffles and phosphorylation at residues Thr 308 and Ser 473 and increased kinase activity. In contrast, infection with a SigD deletion mutant did not induce phosphorylation or activity although Akt was translocated to membrane ruffles. Complementation of the SigD deletion strain with a mutant containing a single Cys to Ser mutation (C462S), did not restore the Akt activation phenotype. This residue has previously been shown to be essential for inositol phosphatase activity of the SigD homologue, SopB. Our data indicate a novel mechanism of Akt activation in which the endogenous cellular pathway does not convert membrane-associated Akt into its active form. SigD is also the first bacterial effector to be identified as an activator of Akt.

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Section: Pi3-k Activation and Rapid Translocation Of Akt To The Plasmsupporting

confidence: 54%

Activation of Akt/Protein Kinase B in Epithelial Cells by theSalmonella typhimurium Effector SigD

Steele‐Mortimer

Knodler

Marcus

et al. 2000

Journal of Biological Chemistry

179

244

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“…Coupled with its propensity to invade cultured epithelial cells, this makes it an extremely valuable tool for studying invasion and intracellular survival and has enabled the identi®cation and characterization of many of the factors involved (Finlay and Falkow, 1990;Francis et al, 1992;Galan et al, 1992;Ginocchio et al, 1992;1994;Garcia-del Portillo et al, 1993a;1995;Stein et al, 1996;Hardt et al, 1998). Initial contact of Salmonella with an epithelial cell induces host cell signal transduction cascades and extensive cytoskeletal rearrangements, which lead to the formation of membrane ruf¯es on the cell surface (Finlay et al, 1991;Ruschkowski et al, 1992;Francis et al, 1993;Pace et al, 1993). Ruf¯e formation is mediated by a host cellular pathway that is dependent on the small GTP-binding protein CDC42 and a bacterially encoded Rho GTPase activator, and results in the internalization of bacteria into a unique membrane-bound vacuole (Finlay and Falkow, 1990;Garciadel Portillo et al, 1994;Chen et al, 1996;Hardt et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Biogenesis of Salmonella typhimurium-containing vacuoles in epithelial cells involves interactions with the early endocytic pathway

et al. 1999

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SummaryIn epithelial cells, the intracellular pathogen Salmonella typhimurium resides and replicates within a unique cytoplasmic organelle, the Salmonella-containing vacuole (SCV). In vitro studies have shown that the SCV is a dynamic organelle that selectively acquires lysosomal glycoproteins (lgps) without fusing directly with lyosomes. Here, we have investigated early events in SCV biogenesis using immuno¯uorescence microscopy and epitope-speci®c¯ow cytometry. We show that proteins speci®c to the early endocytic pathway, EEA1 and transferrin receptor (TR), are present on early SCVs. The association of these proteins with SCVs is transient, and both proteins are undetectable at later time points when lgp and vATPase are acquired. Analysis of the fraction of SCVs containing both TR and lamp-1 showed that TR is lost from SCVs as the lgp is acquired, and that these processes occur progressively and not as the result of a single fusion/ ®ssion event. These experiments reveal a novel mechanism of SCV biogenesis, involving previously undetected initial interactions with the early endocytic pathway followed by the sequential delivery of lgp. The pathway does not involve interactions with the late endosome/prelysosome and is distinct from traditional phagocytic and endocytic pathways. Our study indicates that intracellular S. typhimurium occupies a unique niche, branching away from the traditional endocytic pathway between the early and late endosomal compartments.

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“…It has been reported that Salmonella spp. induce their own uptake in macrophages by stimulating cell membrane ruffling [42,43]. In some experiments, cattle DC were incubated for different times with S. typhimurium (strain BRD562) at a ratio of 1:10 together with LY.…”

Section: Tracer Endocytosismentioning

confidence: 99%

Involvement of caveolae in the uptake of respiratory syncytial virus antigen by dendritic cells

Werling¹,

Hope²,

Chaplin

et al. 1999

Journal of Leukocyte Biology

180

144

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The uptake of respiratory syncytial virus (RSV) antigen by cattle dendritic cells was investigated. Pathways of antigen uptake were monitored by flow cytometry using specific tracers and by proliferation assays, which were used to measure the presentation of RSV antigen and ovalbumin. Inhibitors that differentially affected pathways were used to distinguish them. Presentation of RSV antigen, but not ovalbumin, was inhibited by phorbol myristate acetate and filipin, which have been reported to inhibit caveolae, but not by cytochalasin D, amiloride, or mannose. These inhibitors have been reported to block macropinocytosis and other actin-dependent uptake mechanisms, endocytic pathways involving clathrin-coated pits, and the mannose receptor. Furthermore, co-localization of RSV antigen and caveolae was observed by confocal microscopy. Thus, the major route for uptake of RSV antigen by cattle dendritic cells is one mediated by caveolae, adding a pathway of antigen uptake by dendritic cells to those established. J. Leukoc. Biol. 66: 50-58; 1999.

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Ruffles induced by Salmonella and other stimuli direct macropinocytosis of bacteria

Cited by 413 publications

References 28 publications

Activation of Akt/Protein Kinase B in Epithelial Cells by theSalmonella typhimurium Effector SigD

Activation of Akt/Protein Kinase B in Epithelial Cells by theSalmonella typhimurium Effector SigD

Biogenesis of Salmonella typhimurium-containing vacuoles in epithelial cells involves interactions with the early endocytic pathway

Involvement of caveolae in the uptake of respiratory syncytial virus antigen by dendritic cells

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