title: Cleavage of Armadillo/beta-catenin by the caspase DrICE in Drosophila apoptotic epithelial cells.
abstract: BACKGROUND
  During apoptosis cells become profoundly restructured through concerted cleavage of cellular proteins by caspases. In epithelial tissues, apoptotic cells loose their apical/basal polarity and are extruded from the epithelium. We used the Drosophila embryo as a system to investigate the regulation of components of the zonula adherens during apoptosis. Since Armadillo/beta-catenin (Arm) is a major regulator of cadherin-mediated adhesion, we analyzed the mechanisms of Arm proteolysis in apoptosis.
  
  
  RESULTS
  We define early and late apoptotic stages and find that early in apoptosis Dalpha-catenin remains relatively stable, while Arm and DE-cadherin protein levels are strongly reduced. Arm is cleaved by caspases in embryo extracts and we provide evidence that the caspase-3 homolog drICE cleaves Arm in vitro and in vivo. Cleavage by drICE creates a stable protein fragment that remains associated with the plasma membrane early in apoptosis. To further understand the role of caspase-mediated cleavage of Arm, we examined potential caspase cleavage sites and found that drICE cleaves Arm at a unique DQVD motif in the N-terminal domain of the protein. Mutation of the drICE cleavage site in Arm results in a protein that is not cleaved in vitro and in vivo. Furthermore we provide evidence that cleavage of Arm plays a role in the removal of DE-cadherin from the plasma membrane during apoptosis.
  
  
  CONCLUSIONS
  This study defines the specificity of caspase cleavage of Arm in Drosophila apoptotic cells. Our data suggest that N-terminal truncation of Arm by caspases is evolutionarily conserved and thus might provide a principal mechanism involved in the disassembly of adherens junctions during apoptosis.
authors.affiliation: Institut für Genetik, Heinrich Heine Universität, Düsseldorf, Germany. kessler@molgen.mpg.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Kessler
authors.forename: H Arno J
authors.initials: HA
authors.lastname: Müller
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D051186:Armadillo Domain Proteins / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004330:Drosophila / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D051178:alpha Catenin / Q000378:metabolism
chemical_list: C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D015820:Cadherins; D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D014157:Transcription Factors; D051178:alpha Catenin; C081439:alpha-Cat protein, Drosophila; C501889:shg protein, Drosophila; D020169:Caspases; C109171:drICE protein, Drosophila