Microinjection of the <i>Yersinia</i> YopE cytotoxin in mammalian cells induces actin microfilament disruption

Rosqvist, Roland; Forsberg, Åke; Wolf‐Watz, Hans

doi:10.1042/bst0191131

Cited by 153 publications

(245 citation statements)

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“…Thus, high levels of YopK expression somehow blocked the cytotoxic response. YopE-mediated cytotoxicity requires delivery of YopE into the cytosol of the eukaryotic cell (Rosqvist et al, 1991 YPIII(pIB155EL) and YPIII(pIB155HL), respectively. Transcription of both fusions was regulated by calcium, i.e.…”

Section: Resultsmentioning

confidence: 99%

“…Because the YopE-mediated cytotoxic response of eukaryotic cells infected with Yersinia requires translocation of YopE into the cytosol of the cells (Rosqvist et al, 1991(Rosqvist et al, , 1994, it was likely that cells infected with a yopK-mutant strain would contain increased levels of translocated Yop effectors. To investigate this, HeLa cells were infected with different strains of Y. pseudotuberculosis and analysed for translocation of YopE and YopH by indirect immunofluorescence staining followed by confocal laser-scanning microscopy (CLSM) analysis.…”

Section: Yopk Expression Affects Translocation Of Yope and Yophmentioning

confidence: 99%

“…Related type III secretion systems have been identified in several Gram-negative animal and plant pathogens (Groisman and Ochman, 1993;Forsberg et al, 1994b;Van Gijsegem et al, 1993; and it is possible that the strategy for introduction of anti-host factors into eukaryotic cells is also functionally conserved in several of these pathogens. Translocation of Yop effectors by Yersinia has been shown to require the secreted proteins YopB and YopD (Rosqvist et al, 1991;Sory and Cornelis, 1994;Persson et al, 1995;Sory et al, 1995;Hå kansson et al, 1996b). yopB and yopD mutants have intact type III secretion systems but are unable to transport Yop effector proteins into eukaryotic cells.…”

Section: Introductionmentioning

confidence: 99%

“…In Y. pseudotuberculosis and Yersinia enterocolitica, YpkA, YopE, YopH, and YopM have been shown to be translocated (Rosqvist et al, 1991;Sory and Cornelis, 1994;Persson et al, 1995;Sory et al, 1995;Boland et al, 1996;Hå kansson et al, 1996a). YpkA exhibits Ser/Thr protein kinase activity and displays homology with eukaryotic protein kinases (Galyov et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…The kinase activity of YpkA and its localization to the inner surface of the membrane of infected HeLa cells (Hå kansson et al, 1996a) suggest that YpkA acts by interfering with the signal-transduction pathways of eukaryotic cells. The activity of the YopE cytotoxin leads to disruption of actin microfilaments visualized as a characteristic rounding up of the cells (Rosqvist et al, 1991). YopH is a highly potent protein tyrosine phosphatase (Guan and Dixon, 1990;Zhang et al, 1992) that mediates dephosphorylation of host proteins following its translocation (Bliska et al, 1992;Persson et al, 1995;Andersson et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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YopK of Yersinia pseudotuberculosis controls translocation of Yop effectors across the eukaryotic cell membrane

Holmström

Petterson

Rosqvist

et al. 1997

Molecular Microbiology

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SummaryIntroduction of anti-host factors into eukaryotic cells by extracellular bacteria is a strategy evolved by several Gram-negative pathogens. In these pathogens, the transport of virulence proteins across the bacterial membranes is governed by closely related type III secretion systems. For pathogenic Yersinia, the protein transport across the eukaryotic cell membrane occurs by a polarized mechanism requiring two secreted proteins, YopB and YopD. YopB was recently shown to induce the formation of a pore in the eukaryotic cell membrane, and through this pore, translocation of Yop effectors is believed to occur (Hå kansson et al., 1996b). We have previously shown that YopK of Yersinia pseudotuberculosis is required for the development of a systemic infection in mice. Here, we have analysed the role of YopK in the virulence process in more detail. A yopK-mutant strain was found to induce a more rapid YopE-mediated cytotoxic response in HeLa cells as well as in MDCK-1 cells compared to the wild-type strain. We found that this was the result of a cell-contact-dependent increase in translocation of YopE into HeLa cells. In contrast, overexpression of YopK resulted in impaired translocation. In addition, we found that YopK also influenced the YopBdependent lytic effect on sheep erythrocytes as well as on HeLa cells. A yopK-mutant strain showed a higher lytic activity and the induced pore was larger

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Section: Resultsmentioning

confidence: 99%

Section: Yopk Expression Affects Translocation Of Yope and Yophmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

YopK of Yersinia pseudotuberculosis controls translocation of Yop effectors across the eukaryotic cell membrane

Holmström

Petterson

Rosqvist

et al. 1997

Molecular Microbiology

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127

161

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Yersinia enterocolitica-mediated translocation of defined fusion proteins to the cytosol of mammalian cells results in peptide-specific MHC class I-restricted antigen presentation

Rüssmann

Weissmüller

Geginat³

et al. 2000

Eur. J. Immunol.

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Functional conservation of the secretion and translocation machinery for virulence proteins of yersiniae, salmonellae and shigellae.

et al. 1995

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Virulent bacteria of the genera Yersinia, Shigella and Salmonella secrete a number of virulence determinants, Yops, Ipas and Sips respectively, by a type III secretion pathway. The IpaB protein of Shigella flexneri was expressed in Yersinia pseudotuberculosis and found to be secreted under the same conditions required for Yop secretion. Likewise, YopE was secreted by the wild‐type strain LT2 of Salmonella typhimurium, but YopE was not secreted by the isogenic invA mutant. Secretion of both IpaB and YopE required their respective chaperones, IpgC and YerA. In addition, yopE‐containing S. typhimurium expressed a YopE‐mediated cytotoxicity on cultured HeLa cells. YopE was detected in the cytosol of the infected HeLa cells and the amount of translocated YopE correlated with the degree of cytotoxicity. Both translocation and cytotoxicity were prevented by the addition of gentamicin. Treatment of HeLa cells with cytochalasin D prior to infection prevented internalization of bacteria, but translocation of YopE was still observed. These results favour the hypothesis that YopE is translocated through the plasma membrane by surface‐located bacteria. We propose that virulent Salmonella and Shigella deliver virulence effector molecules into the target cell through the utilization of a functionally conserved secretion/translocation machinery similar to that shown for Yersinia.

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Microinjection of the Yersinia YopE cytotoxin in mammalian cells induces actin microfilament disruption

Cited by 153 publications

References 0 publications

YopK of Yersinia pseudotuberculosis controls translocation of Yop effectors across the eukaryotic cell membrane

YopK of Yersinia pseudotuberculosis controls translocation of Yop effectors across the eukaryotic cell membrane

Yersinia enterocolitica-mediated translocation of defined fusion proteins to the cytosol of mammalian cells results in peptide-specific MHC class I-restricted antigen presentation

Functional conservation of the secretion and translocation machinery for virulence proteins of yersiniae, salmonellae and shigellae.

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