The formation of stable rhodopsin-arrestin complexes induces apoptosis andphotoreceptor cell degeneration

Although many different mutations in humans and Drosophila cause retinal de generation, in most cases, a molecular mechanism for the degeneration has n ot been found. We now demonstrate the existence of stable, persistent compl exes between rhodopsin and its regulatory protein arrestin in several diffe rent retinal degeneration mutants. Elimination of these rhodopsin-arrestin complexes by removing either rhodopsin or arrestin rescues the degeneration phenotype. Furthermore, we show that the accumulation of these complexes t riggers apoptotic cell death and that the observed retinal degeneration req uires the endocytic machinery. This suggests that the endocytosis of rhodop sin-arrestin complexes is a molecular mechanism for the initiation of retin al degeneration. We propose that an identical mechanism may be responsible for the pathology found in a subset of human retinal degenerative disorders .