Abl kinases regulate actin comet tail elongation via an N-WASP-dependent pathway.

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

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