Microtubules are involved in actin-based protrusion at the leading-edge lam
ellipodia of migrating fibroblasts. Here we show that the growth of microtu
bules induced in fibroblasts by removal of the microtubule destabilizer noc
odazole activates Rad GTPase, leading to the polymerization of actin in lam
ellipodial protrusions. Lamellipodial protrusions are also activated by the
rapid growth of a disorganized array of very short microtubules induced by
the microtubule-stabilizing drug taxol. Thus, neither microtubule shorteni
ng nor long-range microtubule-based intracellular transport is required for
activating protrusion. We suggest that the growth phase of microtubule dyn
amic instability at leading-edge lamellipodia locally activates Rad to driv
e actin polymerization and lamellipodial protrusion required for cell migra
tion.