Beyond apoptosis: Caspase regulatory mechanisms and functions in vivo

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.