DISMANTLING CELL-CELL CONTACTS DURING APOPTOSIS IS COUPLED TO A CASPASE-DEPENDENT PROTEOLYTIC CLEAVAGE OF BETA-CATENIN

Cell death by apoptosis is a tightly regulated process that requires c oordinated modification in cellular architecture. The caspase protease family has been shown to play a key role in apoptosis. Here we report that specific and ordered changes in the actin cytoskeleton take plac e during apoptosis. In this context, we have dissected one of the firs t hallmarks in cell death, represented by the severing of contacts amo ng neighboring cells. More specifically, we provide demonstration for the mechanism that could contribute to the disassembly of cytoskeletal organization at cell-cell adhesion. In fact, beta-catenin, a known re gulator of cell-cell adhesion, is proteolytically processed in differe nt cell types after induction of apoptosis. Caspase-3 (cpp32/apopain/y ama) cleaves in vitro translated beta-catenin into a form which is sim ilar in size to that observed in cells undergoing apoptosis. beta-Cate nin cleavage, during apoptosis in vivo and after caspase-3 treatment i n vitro, removes the amino- and carboxy-terminal regions of the protei n. The resulting beta-catenin product is unable to bind alpha-catenin that is responsible for actin filament binding and organization. This evidence indicates that connection with actin filaments organized at c ell-cell contacts could be dismantled during apoptosis. Our observatio ns suggest that caspases orchestrate the specific and sequential chang es in the actin cytoskeleton occurring during cell death via cleavage of different regulators of the microfilament system.