Colchicine activates actin polymerization by microtubule depolymerization.
Swiss 3T3 fibroblasts were treated with the microtubule-disrupting agent colchicine to study any interaction between microtubule dynamics and actin polymerization. Colchicine increased the amount of filamentous actin (F-actin), in a dose- and time-dependent manner with a significant increase at 1 h by about 130% over control level. Confocal microscopic 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 lysophosphatidic acid did, indicating that colchicine may have a different mechanism of actin polymerization regulation from LPA. A variety of microtubule-disrupting agents stimulated actin polymerization in Swiss 3T3 and Rat-2 fibroblasts as did colchicine, but the microtubule-stabilizing agent taxol inhibited actin polymerization induced by the above microtubule-disrupting agents. In addition, colchicine-induced actin polymerization was blocked by two protein phosphatase inhibitors, okadaic acid and calyculin A. These results suggest that microtubule depolymerization activates stress fiber formation by serine/threonine dephosphorylation in fibroblasts.
Jung
H I
HI
Biomolecule Research Group, Korea Basic Science Institute, Taejon, Korea.
Shin
I
I
Park
Y M
YM
Kang
K W
KW
Ha
K S
KS
D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008387:Marine Toxins; D051379:Mice; D008870:Microtubules / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D000199:Actins; D001704:Biopolymers; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D010080:Oxazoles; D019319:Okadaic Acid; D013912:Threonine; D012694:Serine; C059041:calyculin A; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D010738:Type C Phospholipases; D010739:Phospholipase D; D003078:Colchicine