title: Abl kinases regulate actin comet tail elongation via an N-WASP-dependent pathway.
abstract: 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.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Burton
authors.forename: Timothy N
authors.initials: TN
authors.lastname: Oliver
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Pendergast
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D018938:Caco-2 Cells; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D016315:Proto-Oncogene Proteins c-abl / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012763:Shigella flexneri / Q000472:pathogenicity; D014443:Tyrosine / Q000737:chemistry
chemical_list: D000199:Actins; D011994:Recombinant Proteins; D014443:Tyrosine; D016315:Proto-Oncogene Proteins c-abl