Glycosylation of rhodopsin is necessary for its stability and incorporation into photoreceptor outer segment discs

作者：Murray Anne R; Vuong Linda; Brobst Daniel; Fliesler Steven J; Peachey Neal S; Gorbatyuk Marina S; Naash Muna I; Al Ubaidi Muayyad R^*

来源：Human Molecular Genetics, 2015, 24(10): 2709-2723.

DOI：10.1093/hmg/ddv031

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 RHOhT17M mice is likely the cause of phenotype observed in retinitis pigmentosa patients carrying T17M mutation.

• 出版日期2015-5-15