title: Binding of the Shigella protein IpaA to vinculin induces F-actin depolymerization.
abstract: Shigella flexneri, the causative agent of bacillary dysentery, enters into epithelial cells by a macropinocytic process. IpaA, a Shigella protein secreted upon cell contact, binds to the focal adhesion protein vinculin and is required for efficient bacterial uptake. IpaA was shown here to bind with high affinity to the N-terminal residues 1-265 of vinculin. Using co-sedimentation and solid-phase assays, we demonstrated that binding of IpaA to vinculin strongly increases the association of vinculin with F-actin. We also characterized a depolymerizing activity on actin filaments associated with the vinculin-IpaA complex both in vitro and in microinjected cells. We propose that the conformational change of vinculin induced by IpaA binding allows interaction of the vinculin-IpaA complex with F-actin and subsequent depolymerization of actin filaments.
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: R
authors.initials: R
authors.lastname: Bourdet-Sicard
authors.forename: M
authors.initials: M
authors.lastname: Rüdiger
authors.forename: B M
authors.initials: BM
authors.lastname: Jockusch
authors.forename: P
authors.initials: P
authors.lastname: Gounon
authors.forename: P J
authors.initials: PJ
authors.lastname: Sansonetti
authors.forename: G T
authors.initials: GT
authors.lastname: Nhieu
mesh_terms: D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism*; D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D002645:Chickens; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D008845:Microinjections; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D012763:Shigella flexneri / Q000378:metabolism*; D016596:Vinculin / Q000378:metabolism*
chemical_list: D000199:Actins; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C063664:IpaA protein, Shigella flexneri; D010446:Peptide Fragments; D016596:Vinculin