While not identical to vertebrate systems, Drosophila phototransduction is similar in several respects, and the power of the genetic system justifies its use as a model. Extensive genetic screens have been conducted by this applicant for genes that can affect the rate of retinal degeneration which follows from altered rhodopsin:arrestin ratios. In all, 350,000 F1 flies screened have yielded 112 new dominant mutations. This innovative approach stands in contrast to the huge effort required to discover phototransduction mutants directly by their ERG phenotypes. There are four specific aims. In the first aim, the applicant will study the ten new arrestin alleles in the collection by determining the null ERG phenotype, and examining the role of phosphorylation, rhodopsin binding and the function of the arrestin C-terminal domain.
The second aim focuses on the ten new rhodopsin mutants that cause retinal degeneration, some of which do so in a novel light-dependent manner.
The third aim i nvolves the molecular isolation and characterization of a new retinal degeneration locus recovered four times in the screen.
The fourth aim i s to pursue the characterization of the other mutations recovered in the screens.
| Arruda, Susan E; Dolph, Patrick J (2003) Molecular cloning of the pawn locus from Drosophila melanogaster. Gene 310:169-73 |
| Orem, Nicholas R; Dolph, Patrick J (2002) Epitope masking of rhabdomeric rhodopsin during endocytosis-induced retinal degeneration. Mol Vis 8:455-61 |
| Orem, Nicholas R; Dolph, Patrick J (2002) Loss of the phospholipase C gene product induces massive endocytosis of rhodopsin and arrestin in Drosophila photoreceptors. Vision Res 42:497-505 |
| Alloway, P G; Howard, L; Dolph, P J (2000) The formation of stable rhodopsin-arrestin complexes induces apoptosis and photoreceptor cell degeneration. Neuron 28:129-38 |
| Alloway, P G; Dolph, P J (1999) A role for the light-dependent phosphorylation of visual arrestin. Proc Natl Acad Sci U S A 96:6072-7 |
