Year: 2016
Type: dissertation
Abstract: The endoplasmic reticulum is an organelle that responsible for the folding and processing of newly synthesized proteins. When unfolded or misfolded proteins accumulate in the ER and disrupt proper function this leads to a phenomenon known as ER stress. When this occurs, the UPR is activated in order to reduce ER load and restore the ER to its normal function. ATF6, IRE1, and PERK are the three pathways of the UPR. Here, I studied ER stress and the UPR in relation to retinitis pigmentosa, achromatopsia, and retinal degeneration in a tauopathy mouse model. I found that P23H rhodopsin, which is one of the most common mutated proteins involved with the development of retinitis pigmentosa, is highly ubiquitinated by several E3 ubiquitin ligases in order to be targeted for degradation. In addition, knocking out ATF6 seems to increase activation of IRE1 and preserve rhodopsin levels in the case of Rho+/P23H mice. In the achromatopsia study, Class 2 ATF6 mutants experience constitutive transcriptional activation and Class 3 ATF6 mutants are transcriptionally inactive, which can help explain causation of disease development. In the preliminary studies of the PS19 mouse model, I found that there is retinal degeneration and loss of visual function occurring in these mice compared to their wildtype littermates.
Author: Priscilla Chan
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Funders: Research to Prevent Blindness, National Institutes of Health, University of California, San Diego, National Eye Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, School of Medicine, University of California, San Diego
Awards: G1124388078, Regulation of ER stress-induced cell death, G2179675123, University of California San Diego Neuroscience Microscopy Imaging Core, G631213127, G639426234, Endoplasmic Reticulum Stress in Retinal Degeneration, Homeostatic Role of IRE1a-XBP1-PDI1 in Hepatic Lipid Metabolism, G8415332196, G9000057239, G9000064950, G9000082290, G9000098550, G9000103476, G9000263503, Defining Barriers to Gene Therapy, Gene Editing and Silencing in Phototransduction, Cancer Center Support Grant
OpenAlex ID: W2907310168