Disease relevance of yopE

• Temperature sensing in Yersinia pestis: regulation of yopE transcription by lcrF [1].
• Likewise, YopE was secreted by the wild-type strain LT2 of Salmonella typhimurium, but YopE was not secreted by the isogenic invA mutant [2].
• Intracellular membrane localization of pseudomonas ExoS and Yersinia YopE in mammalian cells [3].
• Defined secretion and translocation domains of YopE were fused to the immunodominant T cell Ags listeriolysin O and p60 of Listeria monocytogenes [4].
• Furthermore, we found that either YopE or YopH prevented Listeria invasion, whereas only YopE prevented Edwardsiella and Shigella invasion [5].

High impact information on yopE

• These activities are consistent with previously proposed or demonstrated effects on higher eukaryotes and provide new insights into the roles of these proteins in pathogenesis: SspA in directing formation of membrane ruffles and YopE in arresting cell division [6].
• YopHC403S stabilized focal adhesions, as shown by its dominant-negative effect on focal adhesion disassembly mediated by YopE, a translocated protein which disrupts actin stress fibers [7].
• Treatment of HeLa cells with cytochalasin D prior to infection prevented internalization of bacteria, but translocation of YopE was still observed [2].
• YopE was detected in the cytosol of the infected HeLa cells and the amount of translocated YopE correlated with the degree of cytotoxicity [2].
• These results favour the hypothesis that YopE is translocated through the plasma membrane by surface-located bacteria [2].

Chemical compound and disease context of yopE

• When bound to SycE chaperone in the Yersinia cytoplasm, YopE residues 1-100 are necessary and sufficient for the targeting of hybrid neomycin phosphotransferase [8].
• YopD, the 33-kDa product of the lcrGVHyopBD operon, appears to be involved in delivering YopE and YopH (the Yersinia protein tyrosine phosphatase) into target cells [9].

Biological context of yopE

• Systematic mutagenesis of yopE codons 1 to 7 reveals that, like yopQ, codons 2, 3, 5, and 7 are sensitive to mutagenesis, thereby defining the first empirical similarity between the secretion signals of two type III secreted substrates [10].
• When introduced into the context of the full-length yopE gene, the single-nucleotide mutation reduces the type III injection of YopE into HeLa cells, even though the predicted amino acid sequence remains the same [10].
• In contrast, a mutant no longer making YopE or YopH (a tyrosine phosphatase) induces apoptosis in macrophages similar to wild type [11].
• SycE, a compact, globular dimer with a novel fold, has two large hydrophobic surface patches that may form binding sites for YopE or other type III components [12].
• Pathogenic Yersinia enterocolitica produces two virulence plasmid-encoded cytotoxins, YopE and YopT, that are translocated into target cells where they disrupt the actin cytoskeleton [13].

Anatomical context of yopE

• To understand the functional role of YopE, in vivo studies of the GAP activity in infected eukaryotic cells were conducted [14].
• After oral inoculation of mice, Yersinia pseudotuberculosis yopE and yopH mutants colonize the intestines and Peyer's patches in single-strain infections but fail to persist in competition with wild-type Y. pseudotuberculosis, indicating that these two infection models provide different insights into the roles of Yops [15].
• Translocation of YopE and YopH across host cell's membranes was also dependent on the secretion of YopB and YopD by the same bacterium [16].
• YopE and YopT contribute to antiphagocytic effects by inactivating GTPases controlling cytoskeleton dynamics [17].
• Upon infection of cultured epithelial cells, extracellular Yersinia pseudotuberculosis and Yersinia enterocolitica translocate cytotoxin YopE across the host cell plasma membrane [16].

Associations of yopE with chemical compounds

• Conversely, YopH destabilized focal adhesions, even in the absence of YopE, as shown by loss of phosphotyrosine staining [7].
• As compared with wild-type SycE, glutathione S-transferase-SycE bound and stabilized YopE in the bacterial cytoplasm but failed to release the polypeptide for export by the type III machinery [18].
• YopE has an arginine finger motif showing homology with those found in other GAP proteins [19].
• The results demonstrate that amphipathic N-terminal sequences, containing four or five serine residues, have a much greater probability than hydrophobic or hydrophilic sequences to target YopE for secretion [20].
• Exchange of arginine 144 with alanine, located in this arginine finger motif, results in an inactive form of YopE that can no longer stimulate GTP hydrolysis by the GTPase [19].

Other interactions of yopE

• Like that of yopQ, the secretion signal of yopE exhibits a bipartite nature [10].
• Finally, competition infections with Y. pseudotuberculosis mutants with various abilities to induce inflammation demonstrated that survival of the yopE, but not the yopH, mutant was consistently decreased in inflamed tissues [15].

Analytical, diagnostic and therapeutic context of yopE

• Bacterial mutants defective in their ability to express YopE are avirulent after oral or intraperitoneal infection but virulent following intravenous injection [21].
• Immunofluorescence localization revealed that YopM, in contrast to YopE, is not only targeted to the cytoplasm but also trafficks to the cell's nucleus by means of a vesicle-associated pathway that is strongly inhibited by brefeldin A, perturbed by monensin or bafilomycin A1 and dependent upon microtubules (decreased by colchicine and nocodazole) [22].
• Immunogold electron microscopy on cryosectioned Y. pseudotuberculosis revealed that YopE is secreted and deposited on the bacterial cell surface when the bacteria are grown in Ca(2+)-depleted media at 37 degrees C. No YopE was detected in the cytoplasm or in the membranes [23].
• J774A.1 cells were infected with Y. pestis KIM5 in the presence of a protective polyclonal anti-LcrV antibody or a nonprotective polyclonal anti-YopM antibody, and delivery of YopH and YopE into the cytoplasm was assayed by immunoblotting [24].
• In this study, we compared the localization of LcrV to that of the targeted proteins YopE and YopM by immunoblot analysis of fractions of Yersinia-infected HeLa cultures or by laser-scanning confocal microscopy of infected monolayers [25].

References