Reichert A, Heintz D, Voelter W, Mihelic M, Faulstich H
Max-Planck-Institut für Medizinische Forschung, Heidelberg, Germany.
FEBS Lett. 1994 Jun 27;347(2-3):247-50. doi: 10.1016/0014-5793(94)00551-6.
Thymosin beta 4 forms a 1:1 complex with actin and thereby prevents polymerization. Rapid formation of filaments from this complex was observed, however, when actin trimers were added. Polymerization can likewise be initiated by the addition of one equivalent of phalloidin or, less effectively, cytochalasin B. Since both toxins, which reportedly support nucleation, have similar effects as the covalently linked actin trimers, it appears that the formation of filaments from the actin-thymosin beta 4 complex depends on the availability of stable actin nuclei. Remarkably, rapid polymerization was also observed if small amounts of myosin S1 were added, suggesting that also myosin, a protein functionally connected with polymeric actin, can serve as a nucleation center. Considering the existence of thymosin beta 4 and related peptides in numerous mammalian tissues, our data suggest that spontaneous formation of microfilaments in non-muscle cells may be regulated at the level of nucleation. Uncontrolled polymerization induced by the formation of phalloidin-stabilized nuclei may explain the acute toxic effects of phalloidin in hepatocytes.
胸腺素β4与肌动蛋白形成1:1复合物，从而阻止聚合反应。然而，当添加肌动蛋白三聚体时，观察到该复合物迅速形成细丝。同样，添加一当量的鬼笔环肽或效果稍差的细胞松弛素B也能引发聚合反应。由于据报道这两种支持成核作用的毒素与共价连接的肌动蛋白三聚体具有相似的作用，因此肌动蛋白-胸腺素β4复合物形成细丝似乎取决于稳定肌动蛋白核的可用性。值得注意的是，如果添加少量肌球蛋白S1也会观察到快速聚合反应，这表明与聚合肌动蛋白功能相关的蛋白质肌球蛋白也可以作为成核中心。考虑到许多哺乳动物组织中存在胸腺素β4和相关肽，我们的数据表明非肌肉细胞中微丝的自发形成可能在成核水平上受到调控。由鬼笔环肽稳定的核形成所诱导的不受控制的聚合反应可能解释了鬼笔环肽对肝细胞的急性毒性作用。
