Association of Helicobacter pylori Vacuolating Toxin (VacA) with Lipid Rafts

Glycosylphosphatidylinositol-anchored Proteins and Actin Cytoskeleton Modulate Chloride Transport by Channels Formed by the Helicobacter pylori Vacuolating Cytotoxin VacA in HeLa Cells

“…That GPI-Ps are not required for VacA cell binding and localization in lipid rafts is in agreement with a recent report showing that, in CHO cells defective in GPI-Ps, VacA was localized in lipid rafts and still able to induce vacuolation (20). Moreover, our results also fit very well with the data of Kuo and Wang (17) showing that there was no difference in VacA binding between wild-type CHO cells, CHO cells treated with PI-PLC, or CHO cells overexpressing the fasI GPI-Ps.…”

“…Treatment of highly sensitive cells to VacA with PI-PLC, 1 which specifically removes proteins anchored to the plasma membrane via a GPI link (19), reduced and delayed VacA-induced cell vacuolation (17,18). It has been furthermore reported that although GPI-Ps were not apparently required directly for the binding of VacA to cells (17,20), the toxin may exploit the GPI-Ps pathway of endocytosis (17). Although GPI-Ps appear to freely diffuse throughout the cell plasma membrane, they may reside preferentially in detergent-resistant membrane domains (named lipid rafts (21)) (22) and, in certain cases, be endocytosed via a clathrin-independent pathway (23).…”

“…Although GPI-Ps appear to freely diffuse throughout the cell plasma membrane, they may reside preferentially in detergent-resistant membrane domains (named lipid rafts (21)) (22) and, in certain cases, be endocytosed via a clathrin-independent pathway (23). In addition, treatment of cells with the cholesterolsequestering drug nystatin or ␤-methylcyclodextrin, known to disrupt lipid rafts, strongly impaired VacA activity (18,20,24). This indicated that lipid rafts are involved in the molecular mechanism of VacA-induced vacuolation.…”

“…This indicated that lipid rafts are involved in the molecular mechanism of VacA-induced vacuolation. Accordingly, it has been shown that VacA is associated with lipid rafts (20,24).…”

Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection

“…Cholesterol, as the major component of membrane rafts, is emerging as an important component of the host cells' recognition of bacterial constituents, including lipopolysaccharide via CD14 (36). In addition, membrane cholesterol plays a specific role in the pathogenicity of the H. pylori cytotoxin VacA (37,38), although the vacA dependence of cholesterol gene expression was not tested in these experiments, as the vacA Ϫ mutant was not analyzed at the 24-h time point. H. pylori induction of cholesterol production in host cells could provide a clue to the putative association between chronic H. pylori infection and atherosclerosis (39).…”