Work

Cell Vacuolation Induced by the VacA Cytotoxin ofHelicobacter pylori Is Regulated by the Rac1 GTPase

Year: 2000

Type: article

Abstract: 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.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.c000153200

Authors: Neil A. Hotchin, Timothy L. Cover, Nasreen Akhtar

Institutions: University of Birmingham, Vanderbilt University

Language: English

Topic: Helicobacter pylori-related gastroenterology studies

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430