Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKC zeta

We describe here a signal transduction pathway controlling the establishmen t of mammalian cell polarity. Scratching a confluent monolayer of primary r at astrocytes leads to polarization of cells at the leading edge. The micro tubule organizing center, the microtubule cytoskeleton, and the Golgi reorg anize to face the new free space, and directed cell protrusion and migratio n specifically occur perpendicularly to the scratch. We show here that the interaction of integrins with extracellular matrix at the newly formed cell front leads to the activation and polarized recruitment of Cdc42, which in turn recruits and activates a cytoplasmic mPar6/PKC zeta complex. Localize d PKC zeta activity, acting through the microtubule motor protein dynein, i s required for all aspects of induced polarity in these cells.