Negative regulation of the novel norpA(P24) suppressor, diehard4, in the endo-lysosomal trafficking underlies photoreceptor cell degeneration.

ABSTRACT: Rhodopsin has been used as a prototype system to investigate G protein-coupled receptor (GPCR) internalization and endocytic sorting mechanisms. Failure of rhodopsin recycling upon light activation results in various degenerative retinal diseases. Accumulation of internalized rhodopsin in late endosomes and the impairment of its lysosomal degradation are associated with unregulated cell death that occurs in dystrophies. However, the molecular basis of rhodopsin accumulation remains elusive. We found that the novel norpA(P24) suppressor, diehard4, is responsible for the inability of endo-lysosomal rhodopsin trafficking and retinal degeneration in Drosophila models of retinal dystrophies. We found that diehard4 encodes Osiris 21. Loss of its function suppresses retinal degeneration in norpA(

SUBMITTER: Lee J 

PROVIDER: S-EPMC3674991 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature