Walking a fine caspase line

Walking a fine caspase line W hether caspase enzymes perform developmental tasks or cause cell death can depend on the timing with which a caspase inhibitor protein turns over, fi nd Koto et al. They show that the inhibitor protein follows a dramatic temporal regulation specifi c 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 fl uorescent 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. T he same protein that directs the biogenesis of peroxi-somes, essential detoxifi ers of the cell, also hitches the organelle to its myosin motor for transport into daughter cells, show Chang et al. The beloved model Saccharo-myces cerevisiae does have limita-tions—one being that its peroxisome receptor for the myosin V motor has no known homologues outside of this fungus family. To fi gure out how other eukaryotes accomplish peroxisome inheritance, Chang et al. turned to the yeast Yarrowia lipolytica and a new player, Pex3B. Pex3B was recently identifi ed as a paralogue of Pex3, the highly conserved protein responsible for the earliest stages of peroxisome genesis—forming new membrane at the ER. Chang et al. found that, like Pex3, Pex3B is a peroxisomal integral membrane protein. Deleting Pex3B …