Intermediate filaments

Cytokeratins, the intermediate filament proteins of epithelial cells, are necessary for the structural support of cells. During apoptosis, cytokeratin-and vimentin-containing intermediate filaments reorganize into granular structures (20, 23-25), as is illustrated in Figure I. This process seems to be governed mainly by (hyper)phosphorylation of the cytokeratins during apoptosis (26).

Furthermore, it has been shown that phosphorylation and dephosphoryl-ation events also critically control cell junction assembly and stability and also regulate the formation of the cadherin-cytoskeleton complex (27, 28), thus influencing the adhesive properties of cells.

Recently Caulin et al. (24) and Leers et al. (25) showed that intermediate filament proteins are cleaved by caspases during apoptosis. A conserved caspase-6 motif is found in the linker-2 region of all intermediate filament proteins, except for the type II cytokeratins. Cytokeratin 18 has an additional caspase cleavage site at the C-terminus. as was suggested by Caulin et ai. (24) and recently identified as the DALD motif by Leers et at. (25). The functional significance of the co-ordinated breakdown of the cytokeratins remains unknown. Caulin et a I. (24) suggest that proteolytic cleavage of these intermediate filaments, which are highly polymerized and are relatively insoluble

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Figure t. Linear projections of stacks of confocal scanning laser microscopy images of an apoptotic MR65 lung cancer cell after annexin V labelling, fixation, and staining with the M30 cytodeath antibody: (a) annexin V labelling, (b) aggregated cytokeratin 18 fragments. Apoptosis was induced by 6 h exposure of the cells to 50 roscovitine.

Figure t. Linear projections of stacks of confocal scanning laser microscopy images of an apoptotic MR65 lung cancer cell after annexin V labelling, fixation, and staining with the M30 cytodeath antibody: (a) annexin V labelling, (b) aggregated cytokeratin 18 fragments. Apoptosis was induced by 6 h exposure of the cells to 50 roscovitine.

in normal aqueous solutions, is necessary for the formation of apoptotic bodies.

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