Autophagy-Dependent Rhodopsin Degradation Prevents Retinal Degeneration in Drosophila
| Autor: | Emiko Suzuki, Yoshimi Hinohara, Miki Yamamoto-Hino, Satoshi Goto, Ryosuke Midorikawa, Ryu Ueda, Wakae Awano |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Retinal degeneration
Rhodopsin Time Factors Light Endosome Green Fluorescent Proteins Context (language use) Nerve Tissue Proteins Endosomes Statistics Nonparametric Animals Genetically Modified Microscopy Electron Transmission medicine Autophagy In Situ Nick-End Labeling Animals Drosophila Proteins Microscopy Immunoelectron Diacylglycerol kinase Gene knockdown biology General Neuroscience Retinal Degeneration PPT1 Membrane Proteins rab7 GTP-Binding Proteins Articles medicine.disease Cell biology Disease Models Animal Gene Expression Regulation rab GTP-Binding Proteins Larva Mutation biology.protein Drosophila Photoreceptor Cells Invertebrate RNA Interference Thiolester Hydrolases Lysosomes |
| Popis: | 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 someDrosophilamutants 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 theDrosophilavisual 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 ofatg-7/8orPsd/Eptproduced 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 rescuedPsdknockdown-induced retinal degeneration. Additionally, thePsdknockdown-induced retinal degeneration phenotype was enhanced byPpt1inactivation, 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. |
| Databáze: | OpenAIRE |
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