Abstract
The formation of large perinuclear inclusion bodies containing protein aggregates was first described in HeLa cells. Woijcik et al. (1) have shown that treatment of HeLa cells with the proteasome inhibitor PSI [N-benzyloxycarbonal- Ile-Glu(O-t-butyl)-Ala-leucinal] results in the accumulation of electron- dense material in the vicinity of the Golgi apparatus. These structures were termed proteolysis centers, because ubiquitin as well as components of the 26S proteasome are enriched in inclusion bodies, whereas carbohydrates, lipids, or nucleic acids are not present. Recently, perinuclear inclusion bodies very similar to the ones described by Wojcik et al. (1) have been discovered in other mammalian cell-culture model systems (2-14). These structures were termed "aggresomes," because they mainly consist of high-molecular-weight protein aggregates (1-4,6,7,9-13). Aggresomes also contain proteasomal components and stress proteins, and they are located in close vicinity to the centrosome. Formation of aggresomes in mammalian cells is enhanced upon inhibition of proteasome activity, suggesting that they appear when the capacity of the proteasome is exceeded and the cell has lost the ability to degrade misfolded proteins (1-3,6- 8,10,13). Ultrastructural studies using transmission electron microscopy with immunogold labeling revealed that aggresomes are large membrane-free, spherical structures (diameter approx 1-5 Μm) composed of electron-dense material with an amorphous or fibrillar morphology (1,5,6,10,13). Interestingly, formation of aggresome structures is mostly accompanied by a redistribution of the intermediate filament protein vimentin, which forms a cage around the core of the aggregated, ubiquitinated protein (3,5-7,11,13).
