期刊
MOLECULAR SYSTEMS BIOLOGY
卷 7, 期 -, 页码 -出版社
WILEY
DOI: 10.1038/msb.2011.7
关键词
coatomer; HeLa; Salmonella; siRNA; systems biology
资金
- Bonizzi-Theler foundation
- UBS AG
- Swiss SystemsX.ch initiative
- Direct For Biological Sciences
- Div Of Biological Infrastructure [0965316] Funding Source: National Science Foundation
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. Molecular Systems Biology 7: 474; published online 15 March 2011; doi:10.1038/msb.2011.7
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