Mycalolide B, a novel actin depolymerizing agent.
We investigated the effects of a novel marine toxin, mycalolide B, on actin polymerization and actin-activated myosin Mg(2+)-ATPase activity using purified actin and myosin from rabbit skeletal muscle. The results were compared with cytochalasin D which inhibits actin polymerization by binding to the barbed end of F-actin. By monitoring fluorescent intensity of pyrenyl-actin, mycalolide B did not accelerate actin polymerization but quickly depolymerized F-actin, whereas cytochalasin D accelerated actin nucleation and depolymerized F-actin at slower rate. The kinetics of depolymerization suggest that mycalolide B severs F-actin. The relationship between the concentration of total actin and F-actin at different concentration of mycalolide B suggests that mycalolide B forms 1:1 complex with G-actin. Viscometry and electron microscopic observation further suggest that actin filament was depolymerized by mycalolide B. Unlike cytochalasin D, furthermore, mycalolide B suppressed actin-activated myosin Mg(2+)-ATPase activity. We concluded that mycalolide B severs F-actin and sequesters G-actin and may serve as a novel pharmacological tool for analyzing actin-mediated cell functions.
Saito
S
S
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
Watabe
S
S
Ozaki
H
H
Fusetani
N
N
Karaki
H
H
D000199:Actins / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001704:Biopolymers; D007700:Kinetics; D008387:Marine Toxins / Q000494:pharmacology*; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology*; D011161:Porifera; D011817:Rabbits
D000199:Actins; D001704:Biopolymers; D008387:Marine Toxins; D010080:Oxazoles; C080978:mycalolide B