helicobacter pylori caga disrupts epithelial patterning by activating myosin light chain幽门螺杆菌caga破坏上皮模式通过激活肌球蛋白轻链.pdfVIP

Helicobacter pylori CagA Disrupts Epithelial Patterning by Activating Myosin Light Chain Jonathan B. Muyskens, Karen Guillemin* Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America Abstract Helicobacter pylori infection is a leading cause of ulcers and gastric cancer. We show that expression of the H. pylori virulence factor CagA in a model Drosophila melanogaster epithelium induces morphological disruptions including ectopic furrowing. We find that CagA alters the distribution and increases the levels of activated myosin regulatory light chain (MLC), a key regulator of epithelial integrity. Reducing MLC activity suppresses CagA-induced disruptions. A CagA mutant lacking EPIYA motifs (CagAEPISA) induces less epithelial disruption and is not targeted to apical foci like wild-type CagA. In a cell culture model in which CagAEPISA and CagA have equivalent subcellular localization, CagAEPISA is equally potent in activating MLC. Therefore, in our transgenic system, CagA is targeted by EPIYA motifs to a specific apical region of the epithelium where it efficiently activates MLC to disrupt epithelial integrity. Citation: Muyskens JB, Guillemin K (2011) Helicobacter pylori CagA Disrupts Epithelial Patterning by Activating Myosin Light Chain. PLoS ONE 6(3): e17856. doi:10.1371/journal.pone.0017856 ´ Editor: Stefan Bereswill, Charite-University Medicine Berlin, Germany Received January 9, 2011; Accepted February 10, 2011; Published March 21, 2011 Copyright: 2011 Muyskens, Guillemin. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This project was supported by National Institutes of Health (NIH) grant n