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PMID: 17170705 Published · ppublish English Journal Article

Unfolded protein response in a Drosophila model for retinal degeneration.

The EMBO journal ·Vol. 26 ·No. 1 ·2007-01-10 ·Pages 242-52

Ryoo HD, Domingos PM, Kang MJ, Steller H

Abstract

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.

MeSH Terms
Alternative Splicing Animals Base Sequence Cytoplasm/metabolism DNA-Binding Proteins/genetics,physiology Disease Models, Animal Drosophila Proteins/genetics,physiology Drosophila melanogaster Endoplasmic Reticulum/metabolism Green Fluorescent Proteins/metabolism Molecular Sequence Data Photoreceptor Cells, Invertebrate Protein Denaturation Protein Structure, Tertiary RNA Splicing Retina/metabolism Retinal Degeneration/metabolism
Chemicals
DNA-Binding Proteins Drosophila Proteins Xbp1 protein, Drosophila Green Fluorescent Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ryoo Hyung Don
Department of Cell Biology, NYU School of Medicine, New York, NY 10021, USA.
Domingos Pedro M
Kang Min-Ji
Steller Hermann
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601477
Published
2007-01-10
Epub
2006-00-14
Pages
242-52
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1782370
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7601477 PMC Full Text View journal details
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