Molecular dissection of Salmonella-induced membrane ruffling versus invasion

Hänisch, J. and Ehinger, J. and Ladwein, M. and Rohde, M. and Derivery, E. and Bosse, T. and Steffen, A. and Bumann, D. and Misselwitz, B. and Hardt, W. D. and Gautreau, A. and Stradal, T. E. and Rottner, K.. (2009) Molecular dissection of Salmonella-induced membrane ruffling versus invasion. Cellular Microbiology, 12 (1). pp. 84-98.

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Official URL: http://edoc.unibas.ch/dok/A5259798

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Summary Type III secretion system-mediated injection of a cocktail of bacterial proteins drives actin rearrangements, frequently adopting the shape of prominent protuberances of ruffling membrane, and culminating in host cell invasion of Gram-negative pathogens like Salmonella typhimurium. Different Salmonella effectors are able to bind actin and activate Rho-family GTPases, which have previously been implicated in mediating actin-dependent Salmonella entry by interacting with N-WASP or WAVE-complex, well-established activators of the actin nucleation machine Arp2/3-complex. Using genetic deletion and RNA interference studies, we show here that neither individual nor collective removal of these Arp2/3- complex activators affected host cell invasion as efficiently as Arp2/3-complex knock-down, although the latter was also not essential. However, interference with WAVE-complex function abrogated Salmonella-induced membrane ruffling without significantly affecting entry efficiency, actin or Arp2/3-complex accumulation. In addition, scanning electron microscopy images captured entry events in the absence of prominent membrane ruffles. Finally, localization and RNA interference studies indicated a relevant function in Salmonella entry for the novel Arp2/3-complex regulator WASH. These data establish for the first time that Salmonella invasion is separable from bacteria-induced membrane ruffling, and uncover an additional Arp2/3-complex activator as well as an Arp2/3-complex-independent actin assembly activity that contribute to Salmonella invasion.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Bumann)
UniBasel Contributors:Bumann, Dirk
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Nov 2017 11:18
Deposited On:22 Mar 2012 13:23

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