title: Bacterial signals and cell responses during Shigella entry into epithelial cells.
abstract: Shigella invades epithelial cells by inducing cytoskeletal reorganization localized at the site of bacterial-host cell interaction. During entry, the Shigella type III secretion apparatus allows the insertion of a pore that contains the IpaB and IpaC proteins into cell membranes. Insertion of this complex is thought to allow translocation of the carboxy-terminus moiety of IpaC, but also of other Shigella effectors, such as IpaA, into the cell cytosol. IpaC triggers actin polymerization and the formation of filopodial and lamellipodial extensions dependent on the Cdc42 and Rac GTPases. IpaA, on the other hand, binds to the focal adhesion protein vinculin and induces depolymerization of actin filaments. IpaA and the GTPase Rho are not required for actin polymerization at the site of bacterial contact with the cell membrane, but allow the transformation of the IpaC-induced extensions into a structure that is productive for bacterial entry. Rho is required for the recruitment at entry foci of ezrin, a cytoskeletal linker required for Shigella entry, and also of the Src tyrosine kinase. The Src tyrosine kinase activity, which is required for Shigella-induced actin polymerization, also appears to be involved in a negative regulatory loop that downregulates Rho at the site of entry.
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, INSERM U389, Institut Pasteur, Paris, France. gtranvan@pasteur.fr
authors.forename: G
authors.initials: G
authors.lastname: Tran Van Nhieu
authors.forename: R
authors.initials: R
authors.lastname: Bourdet-Sicard
authors.forename: G
authors.initials: G
authors.lastname: Duménil
authors.forename: A
authors.initials: A
authors.lastname: Blocker
authors.forename: P J
authors.initials: PJ
authors.lastname: Sansonetti
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D004405:Dysentery, Bacillary / Q000382:microbiology*; D006367:HeLa Cells / Q000382:microbiology*; D006801:Humans; D012760:Shigella / Q000472:pathogenicity* / Q000502:physiology; D015398:Signal Transduction; D014774:Virulence
chemical_list: D001426:Bacterial Proteins