Premium
Unfolded protein response in a Drosophila model for retinal degeneration
Author(s) -
Ryoo Hyung Don,
Domingos Pedro M,
Kang MinJi,
Steller Hermann
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601477
Subject(s) - xbp1 , unfolded protein response , biology , endoplasmic reticulum , microbiology and biotechnology , drosophila melanogaster , retinal degeneration , neurodegeneration , rna splicing , green fluorescent protein , heat shock protein , genetics , gene , rna , medicine , pathology , disease
Stress in the endoplasmic reticulum (ER stress) and its cellular response, the unfolded protein response (UPR), are implicated in a wide variety of diseases, but its significance in many disorders remains to be validated in vivo . Here, we analyzed a branch of the UPR mediated by xbp1 in Drosophila to establish its role in neurodegenerative diseases. The Drosophila xbp1 mRNA undergoes ire‐1 ‐mediated unconventional splicing in response to ER stress, and this property was used to develop a specific UPR marker, xbp1‐EGFP, in which EGFP is expressed in frame only after ER stress. xbp1‐EGFP responds specifically to ER stress, but not to proteins that form cytoplasmic aggregates. The ire‐1/xbp1 pathway regulates heat shock cognate protein 3 ( hsc3 ), an ER chaperone. xbp1 splicing and hsc3 induction occur in the retina of ninaE G69D −/+, a Drosophila model for autosomal dominant retinitis pigmentosa (ADRP), and reduction of xbp1 gene dosage accelerates retinal degeneration of these animals. These results demonstrate the role of the UPR in the Drosophila ADRP model and open new opportunities for examining the UPR in other Drosophila disease models.