Cell motility: can Rho GTPases and microtubules point the way?

Migrating cells display a characteristic polarization of the actin cytoskel eton. Actin filaments polymerise in the protruding front of the cell wherea s actin filament bundles contract in the cell body, which results in retrac tion of the cell's rear. The dynamic organization of the actin cytoskeleton provides the force for cell motility and is regulated by small GTPases of the Rho family, in particular Rac1, RhoA and Cdc42. Although the microtubul e cytoskeleton is also polarized in a migrating cell, and microtubules are essential for the directed migration of many cell types, their role in cell motility is not well understood at a molecular level. Here, we discuss the potential molecular mechanisms for interplay of microtubules, actin and Rh o GTPase signalling in cell polarization and motility. Recent evidence sugg ests that microtubules locally modulate the activity of Rho GTPases and, co nversely, Rho GTPases might be responsible for the initial polarization of the microtubule cytoskeleton. Thus, microtubules might be part of a positiv e feedback mechanism that maintains the stable polarization of a directiona lly migrating cell.