title: The fate of desmosomal proteins in apoptotic cells.
abstract: Activation of caspases results in the disruption of structural and signaling networks in apoptotic cells. Recent biochemical and cell biological studies have shown that components of the cadherin-catenin adhesion complex in epithelial adherens junctions are targeted by caspases during apoptosis. In epithelial cells, desmosomes represent a second type of anchoring junctions mediating strong cell-cell contacts. Using antibodies directed against a set of desmosomal proteins, we show that desmosomes are proteolytically targeted during apoptosis. Desmogleins and desmocollins, representing desmosome-specific members of the cadherin superfamily of cell adhesion molecules, are specifically cleaved after onset of apoptosis. Similar to E-cadherin, the desmoglein-3 cytoplasmic tail is cleaved by caspases. In addition the extracellular domains of desmoglein-3 and desmocollin-3 are released from the cell surface by a metalloproteinase activity. In the presence of caspase and/or metalloproteinase inhibitors, both cleavage reactions are almost completely inhibited. As reported previously, the desmosomal plaque protein plakoglobin is cleaved by caspase-3 during apoptosis. Our studies now show that plakophilin-1 and two other major plaque proteins, desmoplakin-1 and -2, are also cleaved by caspases. Immunofluorescence analysis confirmed that this cleavage results in the disruption of the desmosome structure and thus contributes to cell rounding and disintegration of the intermediate filament system.
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, University Hospital Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Weiske
authors.forename: T
authors.initials: T
authors.lastname: Schöneberg
authors.forename: W
authors.initials: W
authors.lastname: Schröder
authors.forename: M
authors.initials: M
authors.lastname: Hatzfeld
authors.forename: R
authors.initials: R
authors.lastname: Tauber
authors.forename: O
authors.initials: O
authors.lastname: Huber
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D003896:Desmosomes / Q000378:metabolism*; D006868:Hydrolysis; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence
chemical_list: D008562:Membrane Glycoproteins