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A new rhodopsin R135W mutation induces endoplasmic reticulum stress and apoptosis in retinal pigment epithelial cells
Author(s) -
Yu Yixin,
Xia Xiaobo,
Li Haibo,
Zhang Yangzhou,
Zhou Xiaoyun,
Jiang Haibo
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28100
Subject(s) - rhodopsin , endoplasmic reticulum , unfolded protein response , retinitis pigmentosa , microbiology and biotechnology , apoptosis , transfection , retinal , biology , chaperone (clinical) , biochemistry , gene , medicine , pathology
Rhodopsin mutations are associated with the autosomal‐dominant form of retinitis pigmentosa (RP). Here we report simultaneous occurrence of RP associated with bilateral nanophthalmos and acute angle‐closure glaucoma in patient with a new mutation in rhodopsin (R135W). ARPE‐19 cells were transfected with myc‐tagged wild‐type (WT) and R135W rhodopsin constructs. The half‐life of WT and R135W rhodopsin was analyzed via cycloheximide chase analysis. We found that R135W rhodopsin was accumulated in the endoplasmic reticulum (ER) and induced unfolded protein response (UPR) and apoptosis. Moreover, chaperone HSP70 alleviated ER stress and prevented apoptosis induced by R135W rhodopsin by attenuating UPR signaling. These findings reveal the novel pathogenic mechanism of RP and suggest that chaperone HSP70 has potential therapeutic significance for RP.