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Originally published In Press as doi:10.1074/jbc.M105769200 on August 10, 2001

J. Biol. Chem., Vol. 276, Issue 44, 41175-41181, November 2, 2001
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The Fate of Desmosomal Proteins in Apoptotic Cells*

Jörg WeiskeDagger , Torsten Schöneberg§, Werner Schröder, Mechthild Hatzfeld||, Rudolf TauberDagger , and Otmar HuberDagger **

From the Dagger  Institute of Clinical Chemistry and Pathobiochemistry, University Hospital Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, the § Institute of Pharmacology, Thielallee 69-73, 14195 Berlin, the  Institute of Biochemistry, Fabeckstrasse 36A, 14195 Berlin, and the || Molecular Biology Group, Medical Faculty of the University of Halle, 06097 Halle, Germany

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.


* This work was supported by grants from the Volkswagen Foundation and the Sonnenfeld Foundation and by Grant HU881/1-1 from the Deutsche Forschungsgemeinschaft.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

** To whom correspondence should be addressed: Institut für Klinische Chemie und Pathobiochemie, Universitätsklinikum Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. Tel.: 49-30-8445-2525; Fax: 49-30-8445-4152; E-mail: otmar.huber@medizin.fu-berlin.de.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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