McKinnon P J, Burgoyne L A
Eur J Cell Biol. 1985 Nov;39(1):161-6.
Cells derived from individuals with the ataxia-telangiectasia syndrome demonstrate a number of unusual properties. They are highly sensitive to the lethal effects of ionizing radiation and also fail to demonstrate the normal inhibition of DNA synthesis associated with this type of DNA-damaging agent. Additionally, a number of ataxia-telangiectasia lymphoblastoid lines have been shown to have an unusual regulation of the cellular actin levels. However, the primary lesion causing ataxia-telangiectasia is unknown. In this paper we report an altered cellular morphology in three ataxia-telangiectasia fibroblast lines, but not in a number of control fibroblast lines. Investigation of the cytoskeleton using antibodies against certain cytoskeletal proteins revealed a difference in the microfilament pattern from ataxia-telangiectasia fibroblasts compared to controls. Ataxia fibroblasts showed a microfilament stress fiber pattern that appeared to have a more well defined and abundant array of stress fibers than control fibroblasts. In contrast, no differences were observed in the microtubule array, nor in the vinculin patterns between any of the cell lines. In addition to the differences in the microfilament patterns, ataxia-telangiectasia fibroblasts differed in their ability to recover from microfilament disruption by dimethyl sulfoxide. Control fibroblasts returned to a normal cellular state in a shorter time compared to ataxia fibroblasts, as judged by indirect immunofluorescence using antiactin. These results provide further evidence for a cytoskeletal anomaly in ataxia-telangiectasia.
患有共济失调毛细血管扩张症综合征的个体所衍生的细胞表现出许多异常特性。它们对电离辐射的致死效应高度敏感，并且也无法表现出与这种DNA损伤剂相关的正常DNA合成抑制。此外，一些共济失调毛细血管扩张症淋巴母细胞系已被证明对细胞肌动蛋白水平有异常调节。然而，导致共济失调毛细血管扩张症的原发性损伤尚不清楚。在本文中，我们报告了三个共济失调毛细血管扩张症成纤维细胞系中细胞形态的改变，但在多个对照成纤维细胞系中未观察到这种改变。使用针对某些细胞骨架蛋白的抗体对细胞骨架进行研究发现，与对照相比，共济失调毛细血管扩张症成纤维细胞的微丝模式存在差异。共济失调成纤维细胞显示出一种微丝应力纤维模式，与对照成纤维细胞相比，其应力纤维排列似乎更明确且更丰富。相比之下，在任何细胞系之间的微管排列或纽蛋白模式方面均未观察到差异。除了微丝模式的差异外，共济失调毛细血管扩张症成纤维细胞在从二甲基亚砜引起的微丝破坏中恢复的能力方面也存在差异。使用抗肌动蛋白进行间接免疫荧光检测发现，与共济失调成纤维细胞相比，对照成纤维细胞在更短的时间内恢复到正常细胞状态。这些结果为共济失调毛细血管扩张症中的细胞骨架异常提供了进一步的证据。
