Molecular dissection of Salmonella-induced membrane ruffling versus invasion.
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Authors
Hänisch, JanEhinger, Julia
Ladwein, Markus
Rohde, Manfred
Derivery, Emmanuel
Bosse, Tanja
Steffen, Anika
Bumann, Dirk
Misselwitz, Benjamin
Hardt, Wolf-Dietrich
Gautreau, Alexis
Stradal, Theresia E B
Rottner, Klemens
Issue Date
2010-01
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Show full item recordAbstract
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.Citation
Molecular dissection of Salmonella-induced membrane ruffling versus invasion. 2010, 12 (1):84-98 Cell. Microbiol.Affiliation
Helmholtz Centre for Infection Research, Braunschweig, Germany.Journal
Cellular microbiologyPubMed ID
19732055Type
ArticleLanguage
enISSN
1462-5822ae974a485f413a2113503eed53cd6c53
10.1111/j.1462-5822.2009.01380.x
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