title: Cleavage and shedding of E-cadherin after induction of apoptosis.
abstract: Apoptotic cell death induces dramatic molecular changes in cells, becoming apparent on the structural level as membrane blebbing, condensation of the cytoplasm and nucleus, and loss of cell-cell contacts. The activation of caspases is one of the fundamental steps during programmed cell death. Here we report a detailed analysis of the fate of the Ca(2+)-dependent cell adhesion molecule E-cadherin in apoptotic epithelial cells and show that during apoptosis fragments of E-cadherin with apparent molecular masses of 24, 29, and 84 kDa are generated by two distinct proteolytic activities. In addition to a caspase-3-mediated cleavage releasing the cytoplasmic domain of E-cadherin, a metalloproteinase sheds the extracellular domain from the cell surface during apoptosis. Immunofluorescence analysis confirmed that concomitant with the disappearance of E-cadherin staining at the cell surface, the E-cadherin cytoplasmic domain accumulates in the cytosol. In the presence of inhibitors of caspase-3 and/or metalloproteinases, cleavage of E-cadherin was almost completely blocked. The simultaneous cleavage of the intracellular and extracellular domains of E-cadherin may provide a highly efficient mechanism to disrupt cadherin-mediated cell-cell contacts in apoptotic cells, a prerequisite for cell rounding and exit from the epithelium.
authors.affiliation: Departments of Medical Oncology and Tumorimmunology, Max Delbrück Center of Molecular Medicine, Robert-Rössle-Strasse 10, D-13092 Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Steinhusen
authors.forename: J
authors.initials: J
authors.lastname: Weiske
authors.forename: V
authors.initials: V
authors.lastname: Badock
authors.forename: R
authors.initials: R
authors.lastname: Tauber
authors.forename: K
authors.initials: K
authors.lastname: Bommert
authors.forename: O
authors.initials: O
authors.lastname: Huber
mesh_terms: D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D008954:Models, Biological; D011480:Protease Inhibitors / Q000494:pharmacology; D017434:Protein Structure, Tertiary
chemical_list: D015820:Cadherins; D004151:Dipeptides; D006877:Hydroxamic Acids; C092152:N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine, 2-aminoethylamide; D011480:Protease Inhibitors; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D020169:Caspases; D008666:Metalloendopeptidases