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Mol Syst Biol. 2011 Mar 15;7:474. doi: 10.1038/msb.2011.7.

RNAi screen of Salmonella invasion shows role of COPI in membrane targeting of cholesterol and Cdc42.

Author information

  • 1Institute of Microbiology, D-BIOL, ETH Zürich, Zürich, Switzerland.

Abstract

The pathogen Salmonella Typhimurium is a common cause of diarrhea and invades the gut tissue by injecting a cocktail of virulence factors into epithelial cells, triggering actin rearrangements, membrane ruffling and pathogen entry. One of these factors is SopE, a G-nucleotide exchange factor for the host cellular Rho GTPases Rac1 and Cdc42. How SopE mediates cellular invasion is incompletely understood. Using genome-scale RNAi screening we identified 72 known and novel host cell proteins affecting SopE-mediated entry. Follow-up assays assigned these 'hits' to particular steps of the invasion process; i.e., binding, effector injection, membrane ruffling, membrane closure and maturation of the Salmonella-containing vacuole. Depletion of the COPI complex revealed a unique effect on virulence factor injection and membrane ruffling. Both effects are attributable to mislocalization of cholesterol, sphingolipids, Rac1 and Cdc42 away from the plasma membrane into a large intracellular compartment. Equivalent results were obtained with the vesicular stomatitis virus. Therefore, COPI-facilitated maintenance of lipids may represent a novel, unifying mechanism essential for a wide range of pathogens, offering opportunities for designing new drugs.

© 2011 EMBO and Macmillan Publishers Limited

PMID:
21407211
[PubMed - indexed for MEDLINE]
PMCID:
PMC3094068
Free PMC Article

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