Accumulation of Rhodopsin in Late Endosomes Triggers Photoreceptor Cell Degeneration
Figure 6
A model for light-dependent retinal degeneration.
In wild type flies, Rh1 is endocytosed upon light-activation. The endocytosed Rh1 undergoes regular lysosomal turnover. In norpA flies, a large number of stable Rhodopsin-Arrestin complexes are formed which undergo rapid endocytosis. Massive endocytosis of Rhodopsin overwhelms the endocytic machinery and this rhodopsin fails to undergo degradation by the lysosomes and hence accumulates in the late endosomes. Endosomal accumulation of Rhodopsin triggers cell death by unknown mechanisms. This condition is simulated in granule group mutants that are defective in lysosomal delivery of endocytosed cargo. In these mutants, Rh1 internalization is similar to that in wild type but Rh1 accumulates in late endosomes as a result of defective trafficking. This accumulation of Rhodopsin also leads to photoreceptor cell death.