Light-induced photoreceptor apoptosis occurs in many forms of inherited ret
inal degeneration resulting in blindness in both vertebrates and invertebra
tes. Though mutations in several photoreceptor signaling proteins have been
implicated in triggering this process, the molecular events relating light
activation of rhodopsin to photoreceptor death are yet unclear. Here, we u
ncover a pathway by which activation of rhodopsin in Drosophila mediates ap
optosis through a G protein-independent mechanism. This process involves th
e formation of membrane complexes of phosphorylated, activated rhodopsin an
d its inhibitory protein arrestin, and subsequent clathrin-dependent endocy
tosis of these complexes into a cytoplasmic compartment Together, these dat
a define the proapoptotic molecules in Drosophila photoreceptors and indica
te a novel signaling pathway for light-activated rhodopsin molecules in con
trol of photoreceptor viability.