Programmed cell death pathways in Drosophila photoreceptors.

摘要

This study explored the mechanisms and events of programmed cell death (PCD) in the Drosophila photoreceptor. To evaluate the role of known PCD agents on adult photoreceptor cell death, the rpr, hid and ced-4 genes were expressed under control of the rhodopsin promoter. The expression of rpr or hid causes rapid cell death of adult photoreceptor cells while expression of ced-4 induces a slower rate of cell death. These results indicate that the rpr, hid and ced-4 responsive PCD pathways are active in the adult photoreceptor. To evaluate the activity of PCD inhibitors, baculoviral p35 and ced-4( K165R) were expressed under control of the rhodopsin promoter. The expression of p35 prevents cell death from rpr and hid expression, but not from ced-4 expression. In contrast, expression of the ced-4(K165R) suppressor delays ced-4-evoked degeneration but not rpr- and hid-evoked degeneration. These results show that expressions of p35 and ced-4( K165R) have suppressive effects on adult photoreceptor PCD. The distinct time courses, morphological details, and responses to the P35 and Ced-4(K165R) suppressors suggest that the rpr and hid responsive PCD pathway is distinct from the ced-4 responsive PCD pathway.; The capability of the p35 and ced-4( K165R) to alter the progression of retinal degeneration in norpA, rdgB and ninaED1 mutants was investigated. Each of these three mutants represents a defect on one key component of the phototransduction process and, thus, is an advantageous model for studying inherited retinal degeneration. Expression of either the p35 or ced-4(K165R) transgene slows, but does not prevent, retinal degeneration in norpA, rdgB and ninaED1 mutants, suggesting that these mutants promote multiple PCD pathways. Given that P35 is a broad range caspase inhibitor, P35-insensitive caspases or caspase-independent mechanism must be involved in the retinal degeneration process in these mutants. Df(H99) mosaic eyes were generated to further show that the Rpr, Hid and Grim driven pathway, which are required for developmental PCD, are not essential of the norpA and rdgB retinal degeneration. These results demonstrate that while developmental PCD pathways are active, novel cell death mechanisms are responsible for norpA, rdgB and ninaE D1 mediated retinal degeneration.