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PMID: 9348292 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Dismantling cell-cell contacts during apoptosis is coupled to a caspase-dependent proteolytic cleavage of beta-catenin.

The Journal of cell biology ·Vol. 139 ·No. 3 ·1997-11-03 ·Pages 759-71

Brancolini C, Lazarevic D, Rodriguez J, Schneider C

Abstract

Cell death by apoptosis is a tightly regulated process that requires coordinated 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 place during apoptosis. In this context, we have dissected one of the first hallmarks in cell death, represented by the severing of contacts among 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 regulator of cell-cell adhesion, is proteolytically processed in different cell types after induction of apoptosis. Caspase-3 (cpp32/apopain/yama) cleaves in vitro translated beta-catenin into a form which is similar in size to that observed in cells undergoing apoptosis. beta-Catenin cleavage, during apoptosis in vivo and after caspase-3 treatment in vitro, removes the amino- and carboxy-terminal regions of the protein. 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 cell-cell contacts could be dismantled during apoptosis. Our observations suggest that caspases orchestrate the specific and sequential changes in the actin cytoskeleton occurring during cell death via cleavage of different regulators of the microfilament system.

MeSH Terms
3T3 Cells Actin Cytoskeleton/metabolism,physiology Actins/metabolism Animals Apoptosis/drug effects,physiology,radiation effects Caspase 3 Caspases Cell Communication/drug effects,physiology,radiation effects Cell Line Cell Survival/physiology Cisplatin/toxicity Cysteine Endopeptidases/metabolism,physiology Cytoskeletal Proteins/metabolism Dogs Hydrolysis Kidney Mice Protein Binding Protein Processing, Post-Translational Signal Transduction Trans-Activators Ultraviolet Rays alpha Catenin beta Catenin
Chemicals
Actins CTNNB1 protein, mouse Ctnna1 protein, mouse Cytoskeletal Proteins Trans-Activators alpha Catenin beta Catenin Casp3 protein, mouse Caspase 3 Caspases Cysteine Endopeptidases Cisplatin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Brancolini C
Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie AREA Science Park, 34142 Trieste, Italy.
Lazarevic D
Rodriguez J
Schneider C
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.139.3.759
Published
1997-11-03
Pages
759-71
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2141701
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.139.3.759 PMC Full Text View journal details
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