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Type: Journal article
Title: BiP prevents rod opsin aggregation
Author: Athanasiou, D.
Kosmaoglou, M.
Kanuga, N.
Novoselov, S.
Paton, A.
Paton, J.
Chapple, J.
Cheetham, M.
Citation: Molecular Biology of the Cell, 2012; 23(18):3522-3531
Publisher: Amer Soc Cell Biology
Issue Date: 2012
ISSN: 1059-1524
Statement of
Dimitra Athanasiou, Maria Kosmaoglou, Naheed Kanuga, Sergey S. Novoselov, Adrienne W. Paton, James C. Paton, J. Paul Chapple and Michael E. Cheetham
Abstract: Mutations in rod opsin—the light-sensitive protein of rod cells—cause retinitis pigmentosa. Many rod opsin mutations lead to protein misfolding, and therefore it is impor¬tant to understand the role of molecular chaperones in rod opsin biogenesis. We show that BiP (HSPA5) prevents the aggregation of rod opsin. Cleavage of BiP with the subtilase cyto¬toxin SubAB results in endoplasmic reticulum (ER) retention and ubiquitylation of wild-type (WT) rod opsin (WT–green fluorescent protein [GFP]) at the ER. Fluorescence recovery after photobleaching reveals that WT-GFP is usually mobile in the ER. By contrast, depletion of BiP activity by treatment with SubAB or coexpression of a BiP ATPase mutant, BiP(T37G), de¬creases WT-GFP mobility to below that of the misfolding P23H mutant of rod opsin (P23H-GFP), which is retained in the ER and can form cytoplasmic ubiquitylated inclusions. SubAB treatment of P23H-GFP–expressing cells decreases the mobility of the mutant protein further and leads to ubiquitylation throughout the ER. Of interest, BiP overexpression increases the mobility of P23H-GFP, suggesting that it can reduce mutant rod opsin aggregation. Therefore inhibition of BiP function results in aggregation of rod opsin in the ER, which suggests that BiP is important for maintaining the solubility of rod opsin in the ER.
Keywords: Cell Line, Tumor; Cytoplasm; Endoplasmic Reticulum; Humans; Subtilisins; Escherichia coli Proteins; Heat-Shock Proteins; Green Fluorescent Proteins; Microscopy, Confocal; Blotting, Western; Fluorescence Recovery After Photobleaching; Transfection; Protein Binding; Protein Transport; Mutation; Ubiquitination; Rod Opsins; Unfolded Protein Response
Rights: © 2012 Athanasiou et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is avail¬able to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (
RMID: 0020122114
DOI: 10.1091/mbc.E12-02-0168
Appears in Collections:Molecular and Biomedical Science publications

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