Lyubimova A, Bershadsky A D, Ben-Ze'ev A
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
J Cell Biochem. 1997 Jun 15;65(4):469-78.
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.
肌动蛋白组装和表达的调控在多种细胞功能（如运动性和黏附）以及定义细胞和组织结构方面具有至关重要的意义。这些生物学过程通过改变聚合态（F）肌动蛋白和可溶性（G）肌动蛋白之间的平衡来控制。先前的研究表明存在一种自调节途径，该途径将肌动蛋白的组装状态和表达联系起来，导致肌动蛋白丝解聚后肌动蛋白合成减少。我们使用了海洋毒素短裸甲藻毒素A和拉春库林A，二者均破坏肌动蛋白细胞骨架的组织，以确定这种自调节反应是由聚合态肌动蛋白水平的降低还是由细胞中单体肌动蛋白浓度的增加所激活。我们发现，在用短裸甲藻毒素A处理的细胞中，丝状肌动蛋白水平降低，并且使用一种可逆交联试剂，我们发现形成了肌动蛋白二聚体。拉春库林A也会使肌动蛋白丝解体，但产生单体肌动蛋白，随后肌动蛋白和纽蛋白的表达减少，而短裸甲藻毒素A处理则提高了这些蛋白质的合成。在用拉春库林A和短裸甲藻毒素A共同处理的细胞中，形成了二聚体肌动蛋白，并且肌动蛋白和纽蛋白的合成高于对照细胞。这些结果表明，赋予肌动蛋白表达自调节性降低的底物是单体肌动蛋白，并且当其二聚体形成导致其水平降低时，肌动蛋白合成增加。
