The Mechanism of Endoplasmic Reticulum Proteostasis and Proteotoxicity in Retinal Degeneration

内质网膜蛋白复合体(EMC)是维持内质网稳态和膜蛋白生物发生的重要因素。使用缺乏EMC的斑马鱼模型，我发现突变的斑马鱼表现出各种视网膜表型，包括光感受器细胞的丧失和视觉功能的缺乏。此外，一条携带报告基因的EMC缺陷斑马鱼实时监测UPR的激活，我发现UPR在受精后3天就被激活了。这一发现得到了批量RNA测序和qPCR分析的进一步证实。这些数据表明，内质网应激和UPR可能在调节与EMC功能障碍相关的视网膜退行性变中发挥关键作用。

ER membrane protein complex (EMC) is an important factor for ER homeostasis maintenance and membrane protein biogenesis. Using an EMC-deficient zebrafish model, I found that mutant fish display various retinal phenotypes, including the loss of photoreceptor cells and lack of visual function. Additionally, an EMC-deficient zebrafish carrying a reporter gene that monitor UPR activation in real time, I found that UPR is activated as early as 3 days post fertilization (dpf). This finding is further confirmed with bulk RNA sequencing analysis and qPCR analysis. These data suggest that ER stress and UPR may play a critical role in regulating retinal degeneration associated with EMC-dysfunction.