Actin disruption is used to study cell functions in vitro (e.g., migration, endocytosis) and in vivo (e.g., tumor cell invasion). Latrunculin A is a bioactive 2-thiazolidinone macrolide derived from sponges that sequesters G-actin and prevents F-actin assembly. It binds monomeric actin with 1:1 stoichiometry and can be used to block actin polymerization both in vitro (Kd = 0.2 μM) and in cells (0.5 μM, 30 min).[1],[2],[3] Latrunculin A (1-10 μM) causes depolymerization of tumor cell cytoskeleton within ten minutes.[4] Overnight treatment of cells with latrunculin A (10 μM) strongly suppresses actin synthesis.[5] Prolonged cell treatment blocks dexamethasone-induced changes in actin cytoskeleton with no effect on cell viability.[6]
Actin是细胞内的一种蛋白质，它参与了许多重要的生物学过程，如细胞迁移和内吞作用。为了研究这些过程，科学家们使用一种叫做Latrunculin A的化合物来干扰actin。Latrunculin A是从海绵中提取出来的2-噻唑啉酮大环化合物，可以结合G-actin并阻止F-actin聚集。它以1:1比例结合单体肌动蛋白，并可用于在体外（Kd = 0.2 μM）和细胞中（0.5 μM, 30 min）阻断肌动蛋白聚合[1] [2] [3]。在10分钟内，Latrunculin A (1-10μM)会导致肿瘤细胞骨架解聚[4]。将细胞长时间处理后(10μM)，能够强烈抑制肌动蛋白的合成[5] 。长时间处理还可以阻止地塞米松诱导对肌动蛋白骨架产生影响而不影响细胞存活率[6]。
References
[1]. Coué, M., Brenner, S.L., Spector, I., et al. Inhibition of actin polymerization by latrunculin A. FEBS Letters 213(2), 316-318 (1987).
[2]. Yarmola, E.G., Somasundaram, T., Boring, T.A., et al. Actin-latrunculin A structure and function. The Journal of Biological Chemisty 275(36), 28120-28127 (2000).
[3]. Loubéry, S., Wilhelm, C., Hurbain, I., et al. Different microtubule motors move early and late endocytic compartments. Traffic 9, 492-509 (2008).
[4]. Hayot, C., Debeir, O., Van Ham, P., et al. Characterization of the activities of actin-affecting drugs on tumor cell migration. Toxicology and Applied Pharmacology 211, 30-40 (2006).
[5]. Lyubimova, A., Bershadsky, A.D., and Ben-Ze'ev, A. Autoregulation of actin synthesis requires the 3'-UTR of actin mRNA and protects cells from actin overproduction. Journal of Cellular Biochemistry 76, 1-12 (1999).
[6]. Liu, X., Wu, Z., Sheibani, N., et al. Low dose latrunculin-A inhibits dexamethasone-induced changes in the actin cytoskeleton and alters extracellular matrix protein expression in cultured human trabecular meshwork cells. Experimental Eye Research 77, 181-188 (2003).