Clostridium difficile toxin B induces reorganization of actin, vinculin, and talin in cultured cells.
Clostridium difficile toxin B induces reorganization of actin, vinculin, and talin in cultured cells.
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DOI：
10.1016/0014-4827(88)90156-5
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发表时间：
1988
影响因子：
3.7
通讯作者：
M. Ottlinger;S. Lin
中科院分区：
文献类型：
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作者：
M. Ottlinger;S. Lin
艰难梭菌毒素B是一种强效的细胞病变剂，可导致培养的动物细胞变圆和树枝状，其作用类似于细胞松弛素诱导的作用。在这项研究中，我们证明了毒素的形态学效应是专门针对肌动蛋白和相关成分的细胞骨架。在细胞形状发生显著变化和微管和中间丝网络发生改变之前，可检测到肌动蛋白应力纤维的剧烈破坏和重组。沿着F-肌动蛋白，粘附斑蛋白，黏着斑蛋白和talin定位在中毒的细胞中的斑片状图案，让人想起在用佛波醇酯处理的细胞或致癌病毒转化的细胞中所看到的。细胞F-肌动蛋白的定量荧光分析表明，这些形态学的变化伴随着适度的净解聚只有15%至20%的肌动蛋白丝在细胞中，解聚与细胞形状的变化密切相关。在对细胞在基质上铺展的补充研究中，我们发现毒素影响肌动蛋白含量和从细胞体延伸的突起的形状。在细胞松弛素处理的细胞，有一个正常的和病毒转化的细胞之间的差异反应扩散毒素的存在。本研究结果支持了C. difficiletoxin B影响一种或多种调节肌动蛋白细胞骨架结构和功能的细胞组分，并且其主要作用是引起应力纤维的显著破坏和F-肌动蛋白的重新定位。
Clostridium difficiletoxin B is a powerful cytopathic agent which causes animal cells in culture to become rounded and arborized, an effect similar to that induced by the cytochalasins. In this study, we demonstrated that the morphological effects of the toxin are directed specifically against the actin and related components of the cytoskeleton. Dramatic disruption and reorganization of the actin stress fibers were detectable prior to significant changes in cell shape and alterations in the microtubular and intermediate filament networks. Along with F-actin, the adhesion plaque proteins, vinculin and talin were localized in intoxicated cells in a patchy pattern reminiscent of that seen in cells treated with phorbol esters or transformed by oncogenic viruses. A quantitative fluorescence assay for cellular F-actin showed that these morphological changes were accompanied by a modest net depolymerization of only 15 to 20% of the actin filaments in the cell, and that depolymerization was closely correlated with changes in cell shape. In complementary studies on cells spreading on a substrate, we found that the toxin affected the actin content and the shape of the processes extended from the cell body. As in cells treated with cytochalasin, there was a differential response between normal and virally transformed cells spreading in the presence of the toxin. The results of this study support the view thatC. difficiletoxin B affects one or more cellular components that regulate the structure and function of the actin cytoskeleton, and that its predominant effect is to cause a dramatic disruption of stress fibers and relocalization of the F-actin.