The host GTPase Dynamin 2 modulates apical junction structure to control cell-to-cell spread of .

The food-borne pathogen uses actin-based motility to generate plasma membrane protrusions that mediate the spread of bacteria between host cells. In polarized epithelial cells, efficient protrusion formation by requires the secreted bacterial protein InlC, which binds to a carboxyl-terminal Src homology 3 (SH3) domain in the human scaffolding protein Tuba. This interaction antagonizes Tuba, thereby diminishing cortical tension at the apical junctional complex and enhancing protrusion formation and spread. Tuba contains five SH3 domains apart from the domain that interacts with InlC. Here, we show that human GTPase Dynamin 2 associates with two SH3 domains in the amino-terminus of Tuba and acts together with this scaffolding protein to control the spread of . Genetic or pharmacological inhibition of Dynamin 2 or knockdown of Tuba each restored normal protrusion formation and spread to a bacterial strain deleted for the gene (∆). Dynamin 2 localized to apical junctions in uninfected human cells and protrusions in cells infected with . Localization of Dynamin 2 to junctions and protrusions depended on Tuba. Knockdown of Dynamin 2 or Tuba diminished junctional linearity, indicating a role for these proteins in controlling cortical tension. Infection with induced InlC-dependent displacement of Dynamin 2 from junctions, suggesting a possible mechanism of antagonism of this GTPase. Collectively, our results show that Dynamin 2 cooperates with Tuba to promote intercellular tension that restricts the spread of ∆. By expressing InlC, wild-type overcomes this restriction.