COLCHICINE ACTIVATES ACTIN POLYMERIZATION BY MICROTUBULE DEPOLYMERIZATION

Swiss 3T3 fibroblasts were treated with the microtubule-disrupting age nt colchicine to study any interaction between microtubule dynamics an d actin polymerization. Colchicine increased the amount of filamentous actin (F-actin), in a dose- and time-dependent manner with a signific ant increase at 1 h by about 130% over control level. Confocal microsc opic observation showed that colchicine increased F-actin contents by stress fiber formation without inducing membrane ruffling. Colchicine did not activate phospholipase C and phospholipase D, whereas lysophos phatidic acid did, indicating that colchicine may have a different mec hanism of actin polymerization regulation from LPA. A variety of micro tubule-disrupting agents stimulated actin polymerization in Swiss 3T3 and Rat-2 fibroblasts as did colchicine, but the microtubule-stabilizi ng agent taxol inhibited actin polymerization induced by the above mic rotubule-disrupting agents. In addition, colchicine-induced actin poly merization was blocked by two protein phosphatase inhibitors, okadaic acid and calyculin A. These results suggest that microtubule depolymer ization activates stress fiber formation by serine/threonine dephospho rylation in fibroblasts.