Abl kinases regulate actin comet tail elongation via an N-WASP-dependent pathway.
Journal Article (Journal Article)
Microbial pathogens have evolved diverse strategies to modulate the host cell cytoskeleton to achieve a productive infection and have proven instrumental for unraveling the molecular machinery that regulates actin polymerization. Here we uncover a mechanism for Shigella flexneri-induced actin comet tail elongation that links Abl family kinases to N-WASP-dependent actin polymerization. We show that the Abl kinases are required for Shigella actin comet tail formation, maximal intracellular motility, and cell-to-cell spread. Abl phosphorylates N-WASP, a host cell protein required for actin comet tail formation, and mutation of the Abl phosphorylation sites on N-WASP impairs comet tail elongation. Furthermore, we show that defective comet tail formation in cells lacking Abl kinases is rescued by activated forms of N-WASP. These data demonstrate for the first time that the Abl kinases play a role in the intracellular motility and intercellular dissemination of Shigella and uncover a new role for Abl kinases in the regulation of pathogen motility.
Full Text
Duke Authors
Cited Authors
- Burton, EA; Oliver, TN; Pendergast, AM
Published Date
- October 2005
Published In
Volume / Issue
- 25 / 20
Start / End Page
- 8834 - 8843
PubMed ID
- 16199863
Pubmed Central ID
- PMC1265773
International Standard Serial Number (ISSN)
- 0270-7306
Digital Object Identifier (DOI)
- 10.1128/MCB.25.20.8834-8843.2005
Language
- eng
Conference Location
- United States