Retinitis pigmentosa‑associated rhodopsin mutant T17M induces endoplasmic reticulum (ER) stress and sensitizes cells to ER stress-induced cell death.

Abstract:

:Retinitis pigmentosa (RP) is a group of inherited diseases that primarily affect light‑sensitive rods and cones in the retina. Rhodopsin mutations, including the T17M mutation, are associated with the autosomal dominant form of retinitis pigmentosa (ADRP) and have been linked to abnormal protein folding. However, the molecular mechanisms underlying T17M rhodopsin‑induced retinal degeneration are yet to be elucidated. In the present study, Human embryonic kidney (HEK) 293 and ARPE‑19 cells were transfected with myc‑tagged wild‑type (WT) and T17M rhodopsin constructs. Cells were fixed and stained with anti‑myc antibodies and the localization of WT and T17M rhodopsin was visualized using immunofluorescence microscopy. Turnover rates of WT and T17M rhodopsin were measured using western blot analysis. In addition, endoplasmic reticulum (ER) stress‑induced cell death was analyzed in WT and T17M rhodopsin‑transfected cells using nuclear staining. Misfolded T17M rhodopsin was observed to be abnormally localized in the ER, while WT rhodopsin was predominantly found at the plasma membrane. Protein turnover analysis revealed that T17M rhodopsin was more rapidly degraded by proteasomes than WT rhodopsin. Furthermore, overexpression of T17M rhodopsin was observed to induce cell death and increase cytotoxicity; predisposing cells to ER stress‑induced cell death. These findings show novel insight into the properties of T17M rhodopsin and highlight the role of ER stress in T17M‑associated RP.

journal_name

Mol Med Rep

authors

Jiang H,Xiong S,Xia X

doi

10.3892/mmr.2014.1987

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

1737-42

issue

5

eissn

1791-2997

issn

1791-3004

journal_volume

9

pub_type

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