Glycosylation of rhodopsin is necessary for its stability and incorporation into photoreceptor outer segment discs
| Autor: | Muna I. Naash, Steven J. Fliesler, Anne R. Murray, Marina S. Gorbatyuk, Daniel Brobst, Muayyad R. Al-Ubaidi, Linda Vuong, Neal S. Peachey |
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| Rok vydání: | 2015 |
| Předmět: |
Retinal degeneration
Rhodopsin Glycosylation genetic structures Mutation Missense Gene Expression Mice Transgenic Mice chemistry.chemical_compound Retinitis pigmentosa Genetics medicine Animals Humans Molecular Biology Genetics (clinical) Retina biology Ubiquitination Retinal Articles General Medicine Rod Cell Outer Segment medicine.disease Photoreceptor outer segment Cell biology carbohydrates (lipids) Disease Models Animal Microscopy Electron medicine.anatomical_structure Biochemistry chemistry Vacuolization biology.protein sense organs Retinitis Pigmentosa |
| Zdroj: | Human Molecular Genetics. 24:2709-2723 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddv031 |
| Popis: | Rhodopsin, a G-protein coupled receptor, most abundant protein in retinal rod photoreceptors, is glycosylated at asparagines-2 and 15 on its N-terminus. To understand the role of rhodopsin's glycosylation in vivo, we generated and characterized a transgenic mouse model that expresses a non-glycosylated form of rhodopsin. We show that lack of glycosylation triggers a dominant form of progressive retinal degeneration. Electron microscopic examination of retinas at postnatal day 17 revealed the presence of vacuolar structures that distorted rod photoreceptor outer segments and became more prominent with age. Expression of non-glycosylated rhodopsin alone showed that it is unstable and is regulated via ubiquitin-mediated proteasomal degradation at the base of outer segments. We observed similar vacuolization in outer segments of transgenic mice expressing human rhodopsin with a T17M mutation (hT17M), suggesting that the mechanism responsible for the degenerative process in mice expressing the non-glycosylated rhodopsin and the RHO(hT17M) mice is likely the cause of phenotype observed in retinitis pigmentosa patients carrying T17M mutation. |
| Databáze: | OpenAIRE |
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