Altered cellular morphology and microfilament array in ataxia-telangiectasia fibroblasts

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.