Rhodopsin homeostasis and retinal degeneration: lessons from the fly

Abstract

Rhodopsins (Rh) are G protein-coupled receptors that function as light-sensors in photoreceptors. In humans, Rh mutations cause retinitis pigmentosa (RP), a degenerative disease that ultimately results in blindness. Studies in Drosophila have provided many insights into basic Rh biology and have identified pathways that lead to retinal degeneration. It has been shown that, because Rh is very abundant in photoreceptors, its accumulation in numerous organelles induces severe stress and results in degeneration of these cells. Moreover, genetic lesions that affect proper activation of membrane-bound Rh lead to disruption in Ca(2+) homeostasis which also causes photoreceptor degeneration. We review here the molecular signals involved in Rh homeostasis and the mechanisms underlying retinal degeneration in flies, and discuss possible links to human diseases.