Bacterial signals and cell responses during Shigella entry into epithelialcells

Shigella invades epithelial cells by inducing cytoskeletal reorganization l ocalized at the site of bacterial-host cell interaction. During entry, the Shigella type III secretion apparatus allows the insertion of a pore that c ontains the IpaB and IpaC proteins into cell membranes. Insertion of this c omplex is thought to allow translocation of the carboxy-terminus moiety of IpaC, but also of other Shigella effectors, such as IpaA, into the cell cyt osol. IpaC triggers actin polymerization and the formation of filopodial an d lamellipodial extensions dependent on the Cdc42 and Rac GTPases. IpaA, on the other hand, binds to the focal adhesion protein vinculin and induces d epolymerization of actin filaments. IpaA and the GTPase Rho are not require d for actin polymerization at the site of bacterial contact with the cell m embrane, 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 Shig ella entry, and also of the Src tyrosine kinase. The Src tyrosine kinase ac tivity, which is required for Shigella-induced actin polymerization, also a ppears to be involved in a negative regulatory loop that downregulates Rho at the site of entry.