Cytochalasins inhibit nuclei-induced actin polymerization by blocking filament elongation.
Polylysine was found to induce polymerization of muscle actin in a low ionic strength buffer containing 0.4 mM MgCl2. The rate of induced polymerization was dependent on the amount and on the molecular size of the polylysine added. A similar effect was obtained by adding actin nuclei (containing about 2-4 actin subunits) cross-linked by p-N,N'-phenylenebismaleimide to G-actin under the same conditions, suggesting that the effect of polylysine is due to promotion of the formation of actin nuclei. Polymerization induced by polylysine and by cross-linked actin nuclei was inhibited by low concentrations (10(-8)-10(-6)M) of cytochalasins. Binding experiments showed that actin filaments, but not actin monomers, contained high-affinity binding sites for [3H]cytochalasin B (one site per 600 actin monomers). The relative affinity of several cytochalasins for these sites (determined by competitive displacement of [3H]dihydrocytochalasin B) was: cytochalasin D greater than cytochalasin E approximately equal to dihydrocytochalasin B. The results of this study suggest that cytochalasins inhibit nuclei-induced actin polymerization by binding to highly specific sites at the point of monomer addition, i.e., the elongation site, in actin nuclei and filaments.
D000199:Actins / Q000378:metabolism*; D001665:Binding Sites; D002474:Cell-Free System; D003571:Cytochalasin B / Q000378:metabolism; D003572:Cytochalasins / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D011107:Polylysine / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D000199:Actins; D003572:Cytochalasins; D008301:Maleimides; D013439:Sulfhydryl Reagents; D011107:Polylysine; D003571:Cytochalasin B; C011328:N,N'-4-phenylenedimaleimide; D008274:Magnesium