Development of a model system for formation of Hirano bodies in cultured mammalian cells
Davis, Richard C
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Hirano Bodies are cytoplasmic rod-shaped paracrystalline F-actin containing structures that have been reported in association with neurodegenerative diseases as well as other conditions including alcoholism,diabetes,and aging.Despite frequent reports in the pathology literature describing the structure of Hirano bodies,little is known regarding their physiological significance.It was shown previously that expression in Dictyostelium of the carboxyl terminal fragment (CT)of the 34 kD protein resulted in formation of Hirano bodies.In mouse fibroblasts, transient expression of the CT fragment induces dramatic reorganization of the actin cytoskeleton. Stress fibers are greatly reduced,and actin filaments appear in a variety of new structures including stellar foci,perinuclear accumulations,and in some cases,a large elliptical mass. These large F-actin rich aggregations are enriched in CT,actin,and cofilin,but not tubulin. Ultrastructural analysis of these aggregations reveals a paracrystalline, ordered filamentous organization,with filament diameter and spacing between 8-12 and 11-15 nm respectively.