A TUMOR PROMOTER INDUCES RAPID AND COORDINATED REORGANIZATION OF ACTIN AND VINCULIN IN CULTURED-CELLS
A TUMOR PROMOTER INDUCES RAPID AND COORDINATED REORGANIZATION OF ACTIN AND VINCULIN IN CULTURED-CELLS
复制标题
DOI：
10.1083/jcb.99.3.1045
复制
发表时间：
1984-01-01
影响因子：
7.8
通讯作者：
EUTENEUER, U
中科院分区：
文献类型：
--
作者：
SCHLIWA, M;NAKAMURA, T;EUTENEUER, U
用有效的肿瘤启动子12- o - tetradecanoylphorol -13-acetate （TPA）处理上皮性非洲绿猴肾（BSC-1）细胞，可诱导肌动蛋白和血管蛋白的快速可逆重新分配，仅在处理2分钟后即可检测到。在20-40分钟内，应力纤维消失，与此同时，在细胞外围和更中心的区域出现了类似褶边的大型含肌动蛋白带。血毒蛋白与这些肌动蛋白带或带呈点状或斑状染色。对基质的粘附从未处理细胞中与应力纤维末端相关的主要局部接触转变为TPA处理后的广泛区域密切接触。高压电镜观察显示，这些条带是由高度交联的肌动蛋白丝网络组成的。研究证实了蛋白与纤维网络的联系，而不是与纤维束的（末端）的联系。微管和静脉蛋白丝的完整性不受TPA处理的影响，但它们的分布被改变以符合高度扭曲的细胞形状。诺可达唑诱导的解聚或紫杉醇诱导的微管稳定既不能阻止也不能改变对TPA的反应。一个完整的中间丝网络似乎也不需要，因为秋碱诱导的静脉蛋白丝向细胞核塌陷并不影响细胞对TPA的反应。肌动蛋白和血管蛋白的快速再分配也发生在去核细胞和环己亚胺存在的情况下，但被二硝基酚或少霉素阻止。tpa诱导的细胞骨架改变不依赖于纤维连接蛋白的表达，也不会被钙调素抑制剂或实验中升高的Ca和cAMP水平所模仿、修饰或阻止。对TPA的形态学反应包括独立于转录和翻译的肌动蛋白和血管蛋白的快速重新分布，Ca或cAMP水平的波动，或微管、中间丝和纤维连接蛋白组织的变化。
Treatment of epithelial African green monkey kidney (BSC-1) cells with the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a rapid and reversible redistribution of actin and vinculin that is detectable after only 2 min of treatment. Within 20-40 min, stress fibers disappear, while at the same time large actin-containing ribbons resembling ruffles develop both at the cell periphery and in more central regions. Vinculin is associated with these actin ribbons or bands in a punctate or patchy staining pattern. Adhesion to the substratum is changed from predominantly focal contacts associated with stress fiber ends in untreated cells to broad zones of close contact after TPA treatment. High voltage EM observations disclose the ribbons to consist of highly cross-linked actin filament networks. An association of vinculin with filament networks, rather than (the ends of) filament bundles, is demonstrated. The integrity of microtubules and vimentin filaments is not affected by TPA treatment, but their distribution is altered to conform with the highly distorted cell shape. The response to TPA is neither prevented nor modified by nocodazole-induced depolymerization or taxol-induced stabilization of microtubules. An intact intermediate filament network seems not required either since colcemid-induced collapse of vimentin filaments towards the nucleus does not affect the cell''s response to TPA. Rapid redistribution of actin and vinculin also takes place in enucleated cells and in the presence of cycloheximide, but is prevented by dinitrophenol or oligomycin. TPA-induced cytoskeletal alterations are independent of fibronectin expression and not mimicked, modified, or prevented by calmodulin inhibitors or experimentally elevated levels of Ca and cAMP. The morphological response to TPA involves rapid redistribution of actin and vinculin independent of transcription and translation, fluctuations in the levels of Ca or cAMP, or changes in the organization of microtubules, intermediate filaments and fibronectin.