Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-47870
Misselwitz, B; Dilling, S; Vonaesch, P; Sacher, R; Snijder, B; Schlumberger, M; Rout, S; Stark, M; von Mering, C; Pelkmans, L; Hardt, W D (2011). RNAi screen of Salmonella invasion shows role of COPI in membrane targeting of cholesterol and Cdc42. Molecular Systems Biology, 7:474.
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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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||07 Faculty of Science > Institute of Molecular Life Sciences|
|DDC:||570 Life sciences; biology|
|Uncontrolled Keywords:||coatomer; HeLa; Salmonella; siRNA; systems biology|
|Deposited On:||07 Apr 2011 09:40|
|Last Modified:||28 Nov 2013 00:45|
|Publisher:||Nature Publishing Group|
|Citations:||Web of Science®. Times Cited: 19|
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