EspT triggers formation of lamellipodia and membrane ruffles through activation of Rac-1 and Cdc42
EspT triggers formation of lamellipodia and membrane ruffles through activation of Rac-1 and Cdc42
Subversion of the eukaryotic cell cytoskeleton is a virulence strategy employed by many bacterial pathogens. Due to the pivotal role of Rho GTPases in actin dynamics they are common targets of bacterial effector proteins and toxins. IpgB1, IpgB2 (Shigella), SifA, SifB (Salmonella) and Map and EspM (attaching and effacing pathogens) constitute a family of type III secretion system effectors that subverts small GTPase signalling pathways. In this study we identified and characterized EspT from Citrobacter rodentium that triggers formation of lamellipodia on Swiss 3T3 and membrane ruffles on HeLa cells, which are reminiscent of the membrane ruffles induced by IpgB1. Ectopic expression of EspT and IpgB1, but not EspM, resulted in a mitochondrial localization. Using dominant negative constructs we found that EspT-induced actin remodelling is dependent on GTP-bound Rac-1 and Cdc42 but not ELMO or Dock180, which are hijacked by IpgB1 in order to form a Rac-1 specific guanine nucleotide exchange factor. Using pull-down assays with the Rac-1 and Cdc42 binding domains of Pak and WASP we demonstrate that EspT is capable of activating both Rac-1 and Cdc42. These results suggest that EspT modulates the host cell cytoskeleton through coactivation of Rac-1 and Cdc42 by a distinct mechanism.
- Imperial College London United Kingdom
- Imperial College United Kingdom
rac1 GTP-Binding Protein, Virulence Factors, Cell Membrane, Molecular Sequence Data, Epithelial Cells, Original Articles, Cell Line, Mice, Bacterial Proteins, Animals, Citrobacter rodentium, Humans, Amino Acid Sequence, Pseudopodia, cdc42 GTP-Binding Protein, Sequence Alignment, Protein Binding
rac1 GTP-Binding Protein, Virulence Factors, Cell Membrane, Molecular Sequence Data, Epithelial Cells, Original Articles, Cell Line, Mice, Bacterial Proteins, Animals, Citrobacter rodentium, Humans, Amino Acid Sequence, Pseudopodia, cdc42 GTP-Binding Protein, Sequence Alignment, Protein Binding
18 Research products, page 1 of 2
- 2012IsAmongTopNSimilarDocuments
- 2005IsAmongTopNSimilarDocuments
- 2014IsAmongTopNSimilarDocuments
- 2018IsRelatedTo
- 2006IsAmongTopNSimilarDocuments
- 2006IsAmongTopNSimilarDocuments
- 2009IsAmongTopNSimilarDocuments
- 2008IsAmongTopNSimilarDocuments
- 2010IsAmongTopNSimilarDocuments
chevron_left - 1
- 2
chevron_right
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).64 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
