Probing mechanisms of cell polarity and membrane trafficking using bacterial effector molecules.

Polarity in mammalian cells emerges from the local assembly of protein interaction networks that control biochemical reactions in space and time. Despite the complexity of these systems however, bacterial pathogens have evolved parsimonious mechanisms to hijack human cell polarity. Here, I will present a tractable model of molecular polarity that is based on the ability of bacterial pathogens to induce localized actin polymerization at the host cell surface. We identify bacterial Type III secreted “effector” molecules that rewire Rho‐family small GTPase signal transduction in space and time. Importantly, molecular polarity is accomplished by assembling proteins onto phospholipid microdomains that function together to generate positive and negative feedback loops. Unexpectedly, our studies indicate that actin polymerization functions as a GTPase signal amplifier involved in generating local membrane protrusive events. By further probing the molecular underpinnings of these biochemical reactions using highly evolved bacterial molecules, we have uncovered principles in cell biology that may be extended to natural cell polarity and membrane trafficking systems.