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Updated: May 25, 2026
In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
Beyond apoptosis: caspase regulatory mechanisms and functions in vivo
1Laboratory for Histogenetic Dynamics, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Abstract:
The caspases, a family of cysteine proteases, function as central regulators of cell death. Recently, caspase activity and caspase substrates identified in the absence of cell death have sparked strong interest in caspase functions in nonapoptotic cellular responses; these functions suggest that caspases may be activated without inducing or before apoptosis, thus leading to the cleavage of a specific subset of substrates. This review focuses primarily on the caspase enzymatic activity. Detailed genetic analyses of caspase-deficient Caenorhabditis elegans, Drosophila, and mice have shown that caspases are essential, not only for controlling the number of cells involved in sculpting or deleting structures in developing animals, but also for dynamic, nonapoptotic cell processes, such as innate immune response, tissue regeneration, cell-fate determination, stem-cell differentiation and neural activation. Our understanding of the spatio-temporal caspase activation mechanisms has advanced, primarily through the study of Drosophila developmental processes. This review will discuss current findings regarding caspase functions in cytoskeletal modification, morphogenetic regulation of cell shape, cell migration and the production of mechanical force during embryogenesis.
Insights
Caspases (cysteine proteases) regulate cell death but also nonapoptotic cellular responses. Genetic studies reveal their essential roles in development, immunity, regeneration, and neural activation, beyond apoptosis.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cell Biology
Background:
- Caspases are cysteine proteases crucial for regulating programmed cell death (apoptosis).
- Emerging evidence highlights caspase roles in nonapoptotic cellular processes, suggesting activation independent of or preceding apoptosis.
- These nonapoptotic functions involve the cleavage of specific substrate sets.
Purpose of the Study:
- To review the enzymatic activity and diverse functions of caspases.
- To explore caspase involvement in nonapoptotic cellular responses and developmental processes.
- To discuss advancements in understanding caspase activation mechanisms and their roles in embryogenesis.
Main Methods:
- Review of genetic analyses in model organisms (C. elegans, Drosophila, mice).
- Analysis of spatio-temporal caspase activation mechanisms, particularly in Drosophila.
- Compilation of current findings on caspase functions in various cellular processes.
Main Results:
- Caspases are essential for cell sculpting and deletion during development.
- Caspases play critical roles in nonapoptotic processes like innate immunity, tissue regeneration, and neural activation.
- Studies in Drosophila have advanced understanding of caspase activation and their roles in embryogenesis.
Conclusions:
- Caspases are multifunctional enzymes with critical roles beyond apoptosis.
- Their involvement spans fundamental processes including development, regeneration, and immunity.
- Further research into caspase activation and nonapoptotic functions is warranted for understanding complex cellular dynamics.
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