Cell vacuolation induced by the VacA cytotoxin of Helicobacter pylori is regulated by the Rac1 GTPase.

Hotchin NA, Cover TL, Akhtar N
J Biol Chem. 2000 275 (19): 14009-12

PMID: 10747859 · DOI:10.1074/jbc.c000153200

Chronic gastric infection with the Gram-negative bacterium Helicobacter pylori is a major contributing factor in the development of duodenal ulcers and is believed to be a significant risk factor in the development of gastric tumors. The VacA cytotoxin of H. pylori is a 90-kDa secreted protein that forms trans-membrane ion channels. In epithelial cells, VacA activity is associated with the rapid formation of acidic vacuoles enriched for late endosomal and lysosomal markers. Rac1 is a member of the Rho family of small GTP-binding proteins that regulate reorganization of the actin cytoskeleton and intracellular signal transduction and are being shown increasingly to play a role in membrane trafficking events. In this study we report that: (i) green fluorescent-tagged Rac1 localizes around the perimeter of the vacuoles induced by VacA; (ii) expression of dominant negative Rac1 in epithelial cells inhibits vacuole formation; (iii) expression of constitutively active Rac1 potentiates the activity of VacA. Taken together, these data demonstrate a role for Rac1 in the regulation of VacA activity.

MeSH Terms (9)

Animals Bacterial Proteins Bacterial Toxins Cell Line Cytotoxins Dogs Helicobacter pylori rac1 GTP-Binding Protein Vacuoles

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