To obtain insight into the molecular dynamics and involvement of microtubules and the related signal molecules in the regulation of cell locomotion, westudied the influence of microtubule disruption on actin stress fibers and focal adhesion assembly in addition to cell morphology. Wefound that all microtubule-disrupting drugs including colcemid and vinblastine rapidly and reversibly induce the formation of actin stress fibers and focal adhesions containing vinculin, accompanied byactivated cell motility in serum-starved Balb/c 3T3cells. In contrast, taxol, a microtubule-stabilizing drug, completely inhibited these effects of the microtubule-disrupting drugs. Amicroinjection of C3 ADP-ribosyltransferase, a specific inhibitor of rho GTPase, blocked the stress fiber and focal adhesion assembly induced bythe microtubule disruption. These results suggested that microtubules contain signal molecules that regulate the formation of stress fibers and focal adhesions byactivating the rho signal cascade. Wepostulate that microtubule-releasing and stress fiber-inducing factors link the intrinsically variable and irregular actin filament dynamics to coordinated and directional locomotion in the process of cell movement.

Cell motility is critically important to manynormal and abnormal biological processes, such as embryonic development, woundhealing, inflammation and cancer metastasis (9, 40). Manybiological active compounds such as growth factors and phorbol esters affect cell motility bydisturbing cytoskeletal networks including ac-tin filaments (10, 1 1, 25). The underlying biological mo-