Department of Cell Biology, New York University School of Medicine 550 First Avenue, New York, NY 10016, USA.
Instituto de Tecnologia Química e Biológica da Universidade Nova de Lisboa, Av. da República, Oeiras 2780-157, Portugal.
Cell Rep. 2018 Feb 6;22(6):1384-1391. doi: 10.1016/j.celrep.2018.01.032.
Rhodopsins require retinoid chromophores for their function. In vertebrates, retinoids also serve as signaling molecules, but whether these molecules similarly regulate gene expression in Drosophila remains unclear. Here, we report the identification of a retinoid-inducible gene in Drosophila, highroad, which is required for photoreceptors to clear folding-defective mutant Rhodopsin-1 proteins. Specifically, knockdown or genetic deletion of highroad blocks the degradation of folding-defective Rhodopsin-1 mutant, ninaE. Moreover, loss of highroad accelerates the age-related retinal degeneration phenotype of ninaE mutants. Elevated highroad transcript levels are detected in ninaE flies, and interestingly, deprivation of retinoids in the fly diet blocks this effect. Consistently, mutations in the retinoid transporter, santa maria, impairs the induction of highroad in ninaE flies. In cultured S2 cells, highroad expression is induced by retinoic acid treatment. These results indicate that cellular quality-control mechanisms against misfolded Rhodopsin-1 involve regulation of gene expression by retinoids.
视蛋白的功能需要类视黄醇作为辅基。在脊椎动物中，类视黄醇也作为信号分子，但这些分子是否以类似的方式调节果蝇中的基因表达尚不清楚。在这里，我们报道了在果蝇中鉴定出一个视黄醇诱导基因 highroad，该基因对于光感受器清除折叠缺陷的突变型 Rhodopsin-1 蛋白是必需的。具体来说，highroad 的敲低或基因缺失会阻止折叠缺陷的 Rhodopsin-1 突变体 ninaE 的降解。此外，highroad 的缺失会加速 ninaE 突变体的年龄相关视网膜变性表型。在 ninaE 果蝇中检测到 highroad 转录本水平升高，有趣的是，在果蝇饮食中去除类视黄醇会阻断这种效应。同样，视黄醇转运蛋白 santa maria 的突变会损害 ninaE 果蝇中 highroad 的诱导。在培养的 S2 细胞中，视黄酸处理可诱导 highroad 的表达。这些结果表明，针对错误折叠的 Rhodopsin-1 的细胞质量控制机制涉及视黄醇对基因表达的调节。
