Boubakri, M., Chaya, T., Hirata, H. et al. (6 more authors) (2016) Loss of ift122, a Retrograde Intraflagellar Transport (IFT) Complex Component, Leads to Slow, Progressive Photoreceptor Degeneration Due to Inefficient Opsin Transport. Journal of Biological Chemistry, 291 (47). pp. 24465-24474. ISSN 0021-9258
Abstract
In the retina, aberrant opsin transport from cell bodies to outer segments leads to retinal degenerative diseases such as retinitis pigmentosa. Opsin transport is facilitated by the intraflagellar transport (IFT) system which mediates the bidirectional movement of proteins within cilia. In contrast to functions of the anterograde transport executed by IFT complex B (IFT-B), the precise functions of the retrograde transport mediated by IFT complex A (IFT-A) have not been well studied in photoreceptor cilia. Here, we analyzed developing zebrafish larvae carrying a null mutation in ift122 encoding a component of IFT-A. Ift122 mutant larvae show unexpectedly mild phenotypes, compared to those of mutants defective in IFT-B. Ift122 mutants exhibit a slow onset of progressive photoreceptor degeneration mainly after 7dpf. Ift122 mutant larvae also develop cystic kidney but not curly body, both of which are typically observed in various ciliary mutants. Ift122 mutants display a loss of cilia in the inner ear hair cells and nasal pit epithelia. Loss of ift122 causes disorganization of outer segment discs. Ectopic accumulation of an IFT-B component, ift88, is observed in the ift122 mutant photoreceptor cilia. In addition, pulse-chase experiments using GFP-opsin fusion proteins revealed that ift122 is required for the efficient transport of opsin and the distal elongation of outer segments. These results show that IFT-A is essential for the efficient transport of outer segment proteins, including opsin, and for the survival of retinal photoreceptor cells, rendering the ift122 mutant a unique model for human retinal degenerative diseases.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Reproduced in accordance with the publisher's self-archiving policy. |
Keywords: | cilia; hair cell; photoreceptor; retinal degeneration; rhodopsin |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Funding Information: | Funder Grant number NATIONAL INSTITUTE OF HEALTH - UNITED STATES OF AMERICA 7R01EY018176-06 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 Feb 2018 11:18 |
Last Modified: | 01 Feb 2018 11:18 |
Published Version: | https://doi.org/10.1074/jbc.M116.738658 |
Status: | Published |
Publisher: | American Society for Biochemistry and Molecular Biology |
Refereed: | Yes |
Identification Number: | 10.1074/jbc.M116.738658 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:126909 |