Drosophila mosaic screen identifies diehard mutants as norpA P24 suppressors

Lee, Jongwoo

doi:10.1007/s13258-012-0097-6

Cited by 1 publication

(2 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The die4 mutant was previously identified as a norpA P24 suppressor from a genetic screen by using eye-specific FLP-FRT mosaic flies [31], delaying degeneration several days (Figure 1G). The die4 mutant was generated using ethyl methanesulfonate (EMS) mutagenesis, possibly bearing multiple mutations.…”

Section: Resultsmentioning

confidence: 95%

“…Because of these complexities, we used multiple mapping methods to identify the exact mutation responsible for the suppressive phenotype of the die4 mutant. We previously reported that the mutation in the cytological region of 32D5 to E4 of the die4 chromosome, is responsible for the suppressive phenotype [31]. Although the die4 chromosome is homozygous lethal, this mutation is viable, in that the genomic deficiency, Exel6028, failed to complement the suppressive phenotype of die4 , and was still viable (Table S1).…”

Section: Resultsmentioning

confidence: 97%

See 1 more Smart Citation

Negative Regulation of the Novel norpAP24 Suppressor, diehard4, in the Endo-lysosomal Trafficking Underlies Photoreceptor Cell Degeneration

2013

Self Cite

View full text Add to dashboard Cite

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 norpAP24 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 norpAP24, rdgC306, and trp1, but not in rdgB2, suggesting a common cause of photoreceptor death. In addition, the loss of Osiris 21 function shifts the membrane balance between late endosomes and lysosomes as evidenced by smaller late endosomes and the proliferation of lysosomal compartments, thus facilitating the degradation of endocytosed rhodopsin. Our results demonstrate the existence of negative regulation in vesicular traffic between endosomes and lysosomes. We anticipate that the identification of additional components and an in-depth description of this specific molecular machinery will aid in therapeutic interventions of various retinal dystrophies and GPCR-related human diseases.

show abstract

Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 97%