Autophagy-Dependent Rhodopsin Degradation Prevents Retinal Degeneration in Drosophila
Open accessAbstract
Recent studies have demonstrated protective roles for autophagy in various neurodegenerative disorders, including the polyglutamine diseases; however, the role of autophagy in retinal degeneration has remained unclear. Accumulation of activated rhodopsin in some Drosophila mutants leads to retinal degeneration, and although it is known that activated rhodopsin is degraded in endosomal pathways in normal photoreceptor cells, the contribution of autophagy to rhodopsin regulation has remained elusive. This study reveals that activated rhodopsin is degraded by autophagy in collaboration with endosomal pathways to prevent retinal degeneration. Light-dependent retinal degeneration in the Drosophila visual system is caused by the knockdown or mutation of autophagy-essential components, such as autophagy-related protein 7 and 8 (atg-7/atg-8), or genes essential for PE (phosphatidylethanolamine) biogenesis and autophagosome formation, including Phosphatidylserine decarboxylase (Psd) and CDP-ethanolamine:diacylglycerol ethanolaminephosphotransferase (Ept). The knockdown of atg-7/8 or Psd/Ept produced an increase in the amount of rhodopsin localized to Rab7-positive late endosomes. This rhodopsin accumulation, followed by retinal degeneration, was suppressed by overexpression of Rab7, which accelerated the endosomal degradation pathway. These results indicate a degree of cross talk between the autophagic and endosomal/lysosomal pathways. Importantly, a reduction in rhodopsin levels rescued Psd knockdown-induced retinal degeneration. Additionally, the Psd knockdown-induced retinal degeneration phenotype was enhanced by Ppt1 inactivation, which causes infantile neuronal ceroid lipofuscinosis, implying that autophagy plays a significant role in its pathogenesis. Collectively, the current data reveal that autophagy suppresses light-dependent retinal degeneration in collaboration with the endosomal degradation pathway and that rhodopsin is a key substrate for autophagic degradation in this context.
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Studies on Drosophila have shown that degradation of rhabdomeral membrane also includes classical autophagy.
“Studies on Drosophila have shown that degradation also includes classical autophagy (Midorikawa et al., 2010).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Midorikawa et al., 2010
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The cell biology of the retinal pigment epithelium
Lakkaraju, A., Umapathy, A., Tan, L. X., Daniele, L., Philp, N. J., Boesze-Battaglia, K., & Williams, D. S. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100846 · Cited by 422 · see citing works
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- Authors
- Midorikawa, R., Yamamoto-Hino, M., Awano, W., Hinohara, Y., Suzuki, E., Ueda, R., & Goto, S.
- Affiliations
- National Institute of Genetics (JP)
- Corresponding author
- Goto, Satoshi
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-08-11
- Volume
- 30
- Issue
- 32
- Pages
- 10703-10719
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6634698
- OpenAlex
- W1969890668
- Cited by
- 63
- References
- 59
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 3 · 2018: 3 · 2016: 5 · 2015: 7 · 2014: 1 · 2013: 5 · 2012: 7
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institute of Genetics
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- autophagy, retinal degeneration, Drosophila photoreceptors, endosomal degradation, lysosomal pathway, Rab7, phosphatidylserine decarboxylase, PPT1, infantile neuronal ceroid lipofuscinosis
- MeSH terms
- rab7 GTP-Binding Proteins, Animals, Autophagy, Disease Models, Animal, Drosophila, Gene Expression Regulation, Larva, Light, Lysosomes, Membrane Proteins, Mutation, Nerve Tissue Proteins, Endosomes, Retinal Degeneration, Rhodopsin, Thiolester Hydrolases, Time Factors, Microscopy, Immunoelectron, Photoreceptor Cells, Invertebrate, Statistics, Nonparametric, In Situ Nick-End Labeling, rab GTP-Binding Proteins, Drosophila Proteins, Animals, Genetically Modified, RNA Interference, Microscopy, Electron, Transmission, Green Fluorescent Proteins
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