Light triggers formation of damaging reactive oxygen species (ROS) in photoreceptor cells. Chartier et al. show that a membrane protein protects cells in the eye and elsewhere in the body by quashing ROS production.
The Drosophila protein Crumbs (Crb) helps polarize epithelial cells, boosting the amount of membrane with apical characteristics. Crb also seems to serve as a cellular guardian. Mutations in one of its human versions cause diseases such as retinitis pigmentosa, which results in tunnel vision and poor night vision. Researchers have reported previously that Crb blocks Rac1, a protein that teams up with the enzyme NADPH oxidase to generate the ROS superoxide. Although cells use superoxide for signaling, in large quantities it can be destructive.
To determine whether Crb provides protection by curtailing ROS, the researchers gauged levels of these damaging molecules in fruit fly epithelial cells. They found that cells without Crb carried more ROS than did control cells. Inhibiting Rac1 or NADPH oxidase in the mutant cells restored their ROS levels to normal. Previous studies showed that loss of Crb causes epithelial layers in the embryo to disintegrate. Chartier et al. discovered that they could prevent this degeneration by engineering the embryos to produce extra amounts of the ROS-neutralizing enzyme Sod1.
The researchers also showed that Crb shields photoreceptor cells in the fly eye. Earlier work revealed that, if Crb is absent, photoreceptor cells die if exposed to light. This team found large quantities of ROS in eyes from flies that lacked Crb only in their eye cells. Feeding these flies compounds that suppress Rac1, NADPH oxidase, or ROS prevented their retinas from degenerating after exposure to light, Chartier et al. reported.