Montell's group studies border cells in the fly egg chamber, which migrate to help establish the sperm entry site. Rac activity is needed for this; so to identify more players, the group screened for proteins that restore migration when Rac activity is reduced. They found DIAP-1. Although DIAP-1 is essential for cell survival in the embryo, its loss in the ovary caused migration defects but not cell death.
Extra actin or profilin, presumably leading to increased actin polymerization, also compensated for the loss of Rac. DIAP-1 may also promote actin polymerization. To block apoptosis, DIAP-1 inhibits the fly caspase-9 homologue, called Dronc. Dronc is probably the DIAP-1 target in border cell migration as well, as reducing its activity suppressed the loss of Rac. Possible Dronc substrates include Rac and actin, which are cleaved by caspases during apoptosis, or profilin.
The unexpected identification of DIAP-1 as a suppressor emphasizes the importance of random screens. “The whole point is to find something that you can't even imagine would be involved,” says Montell. Tumor cells that manage to increase their levels of DIAP-1–like proteins could gain both a survival advantage and the ability to migrate. ▪