Autoregulation of actin synthesis responds to monomeric actin levels.
Regulation of the assembly and expression of actin is of major importance in diverse cellular functions such as motility and adhesion and in defining cellular and tissue architecture. These biological processes are controlled by changing the balance between polymerized (F) and soluble (G) actin. Previous studies have indicated the existence of an autoregulatory pathway that links the state of assembly and expression of actin, resulting in the reduction of actin synthesis after actin filaments are depolymerized. We have employed the marine toxins swinholide A and latrunculin A, both disrupting the organization of the actin-cytoskeleton, to determine whether this autoregulatory response is activated by a decrease in the level of polymerized actin or by an increase in monomeric actin concentrations in the cell. We showed that in cells treated with swinholide A the level of filamentous actin is decreased, and using a reversible cross-linking reagent, we found that actin dimers are formed. Latrunculin A also disassembled actin filaments, but produced monomeric actin, followed by a reduction in actin and vinculin expression, while swinholide A treatment elevated the synthesis of these proteins. In cells treated with both latrunculin A and swinholide A, dimeric actin was formed, and actin and vinculin synthesis were higher than in control cells. These results suggest that the substrate that confers an autoregulated reduction in actin expression is monomeric actin, and when its level is decreased by dimeric actin formation, actin synthesis is increased.
Lyubimova
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Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Bershadsky
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AD
Ben-Ze'ev
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D016475:3T3 Cells; D000199:Actins / Q000096:biosynthesis* / Q000502:physiology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003603:Cytotoxins / Q000494:pharmacology; D019281:Dimerization; D008387:Marine Toxins / Q000494:pharmacology; D051379:Mice; D011487:Protein Conformation / Q000187:drug effects; D012313:RNA / Q000032:analysis; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003603:Cytotoxins; D008387:Marine Toxins; D013844:Thiazoles; D053778:Thiazolidines; D012313:RNA; C086235:swinholide A; C037067:latrunculin A