Listeria Cycle of Propagation

Cell migration: a cyclic process of force generation Membrane-Cyto. Adhesion Resists Extension a PIP2. Sheetz, Nature Rev. MCB. 2:392 (2001) Extracellular Matrix Adhesion Linked to Force Generation by Rearward Flow Cell migration 5 STEP cycle: describe cycle Focus our attention on the 2 STEP extension and attachement Lamellipodial extension and ECM probing involve forces generated by actin: Forward on the memebrane and rearward on integrins Laser tweezers experiments allow us to explore force exerted by the actin reaward flow on integrins Mike already described the effect of forces on the integrin-cytoskeleton interactions Transition: definition of the lamellipodia How do cells locally trans-duce Matrix rigidity into a signal used to direct cell edge extension?

Lamellipodial extension driven by actin assembly Rac-GTPase lamellipodia Difference between the lamellipodia and the lamella Protrusion of the membrane during cell edge extension is driven by actin polymerization and depolymerization. Polymerization at the front Stabilization of the meshwork Depolymerization at the back Relatively constant length and a stationary gradient reflecting a steady-state process of assembly at the front and disassembly at the rear Account for extension, but ECM probing? No myosin Myosin is required for migration and cell spreading The cytoskeletal treadmilling cycle can power actin-based movement of beads or bacteria, without the need for myosin-based contractility Components that will be involved in this talk are LIM kinase, cofilin, Rac GTPase. lamella Actin plolymerization (front) and depolymarization(rear) define the lamellipodial width Forces generated by Myosins? Cell spreading and migration require myosin activity

Model for Propulsion of Listeria

Several Pathogens Co-Opt Actin

Salmonella Injects Critical Proteins

Shigella Targets MTs and Actin

Mycobacteria Modify Actin Dynamics

Enteropathic E. coli Break Contacts