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Whether caspase enzymes perform developmental tasks or cause cell death can depend on the timing with which a caspase inhibitor protein turns over, find Koto et al. They show that the inhibitor protein follows a dramatic temporal regulation specific to cell type and maturity.
In the last decade, researchers realized that the destructive capabilities of caspase enzymes can be harnessed to carry out certain developmental events, such as dendrite pruning and sperm individualization. But how the caspases are put to work in these scenarios without turning deadly remains a mystery.
Koto et al. devised a fluorescent version of the caspase inhibitor DIAP1 to follow its fate in live Drosophila cells during sensory organ bristle development. Surprisingly, the inhibitor vanished altogether in the midst of cell differentiation, without activating cell death, and then reappeared in two cells, including the shaft cell, which spurts forth the bristle. An excess of DIAP1 in the shaft cell gave shorter, thicker bristles, whereas knocking down diap1 resulted in the loss of the shaft cell to programmed cell death. DIAP1's timely reappearance in this cell followed by a second quick departure appears to ensure the delicate balance between caspase-driven bristle formation and the cell death cascade. The nonlethal nature of the DIAP1 disappearances in these cells indicates other survival strategies exist.
The researchers propose that DIAP1's degradation promotes activation of the initiator caspase, Dronc, without waking up the downstream executioner caspases. Whereas other studies have shown non-death caspase activities sequestered to subcellular compartments, this work hints that caspases can also be activated just a touch, before being turned back down.