Binding of the Shigella protein IpaA to vinculin induces F-actin depolymerization

Shigella flexneri, the causative agent of bacillary dysentery, enters into epithelial cells by a macropinocytic process. IpaA, a Shigella protein secr eted 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-sedime ntation and solid-phase assays, we demonstrated that binding of IpaA to vin culin 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 prop ose that the conformational change of vinculin induced by IpaA binding allo ws interaction of the vinculin-IpaA complex with F-actin and subsequent dep olymerization of actin filaments.