Plakin proteins are coordinately cleaved during apoptosis but preferentially through the action of different caspases.
In epithelial cells, cell-cell and cell-matrix junctions, desmosomes and hemidesmosomes, provide anchorage sites for the keratin-intermediate filaments. The plakin proteins desmoplakin (DP), plectin, and periplakin represent intracellular constituents of these adhesion junctions. In staurosporine-treated apoptotic HaCaT cells, DP, plectin, and periplakin became cleaved coordinately with the elimination of keratins 10 and 14, while involucrin, actin, and keratin 18 displayed considerable stability. The caspase inhibitor zVAD-fmk prevented both the cell detachment and protein cleavage, indicating the function of caspases in these events. Closer examination in vitro revealed that while caspases 2 and 4 most efficiently cleaved DP, and plectin served as a target for caspases 3 and 7, periplakin as well as keratins were cleaved by caspase 6. The involvement of multiple caspases in the destruction of epithelial cell integrity ensures the efficient elimination of cytoskeleton, but also provides specificity for selectively targeting individual adhesion molecules.
Aho
Sirpa
S
Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. sirpa.aho@jefferson.edu
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D051180:Desmoplakins; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007381:Intermediate Filament Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D015603:Keratinocytes / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D051179:Plakins; D051190:Plectin; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors
D000590:Amino Acid Chloromethyl Ketones; D003598:Cytoskeletal Proteins; C495294:DSP protein, human; D051180:Desmoplakins; D004791:Enzyme Inhibitors; D007381:Intermediate Filament Proteins; C495332:PLEC protein, human; D051179:Plakins; D051190:Plectin; C110037:Ppl protein, mouse; D011994:Recombinant Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D007633:Keratins; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D019311:Staurosporine