Drosophila as a model for unfolded protein response research.
Drosophila as a model for unfolded protein response research.
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DOI：
10.5483/bmbrep.2015.48.8.099
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发表时间：
2015-08
期刊：
影响因子：
3.8
通讯作者：
Ryoo HD
中科院分区：
文献类型：
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作者：
Ryoo HD
内质网是大多数分泌和膜蛋白合成、折叠和进一步成熟的细胞器。由于许多条件可以干扰这种内质网功能，真核细胞配备了响应信号通路，被广泛称为未折叠蛋白反应(UPR)。UPR不能完全解决的内质网应激的慢性状况，或损害UPR信号本身的状况，与许多代谢性和退行性疾病有关。近年来，果蝇被积极地用来研究UPR和疾病之间的这种联系。值得注意的是，UPR通路在果蝇和人类之间很大程度上是保守的，中介基因对两种生物的发育都是必不可少的，这表明它们需要解决固有的压力。到目前为止，已知许多果蝇基因突变会在内质网中施加压力，其中一些似乎与导致人类疾病的基因相似。此外，研究还采用了在果蝇组织中过度表达人类突变的策略来进行遗传修饰物筛选。基本的UPR途径是保守的，再加上在这个有机体中有许多人类疾病模型可用，这使得果蝇成为研究人类疾病机制的有力工具。[BMB报告2015；48(8)：445-453]
Endoplasmic Reticulum (ER) is an organelle where most secretory and membrane proteins are synthesized, folded, and undergo further maturation. As numerous conditions can perturb such ER function, eukaryotic cells are equipped with responsive signaling pathways, widely referred to as the Unfolded Protein Response (UPR). Chronic conditions of ER stress that cannot be fully resolved by UPR, or conditions that impair UPR signaling itself, are associated with many metabolic and degenerative diseases. In recent years, Drosophila has been actively employed to study such connections between UPR and disease. Notably, the UPR pathways are largely conserved between Drosophila and humans, and the mediating genes are essential for development in both organisms, indicating their requirement to resolve inherent stress. By now, many Drosophila mutations are known to impose stress in the ER, and a number of these appear similar to those that underlie human diseases. In addition, studies have employed the strategy of overexpressing human mutations in Drosophila tissues to perform genetic modifier screens. The fact that the basic UPR pathways are conserved, together with the availability of many human disease models in this organism, makes Drosophila a powerful tool for studying human disease mechanisms. [BMB Reports 2015; 48(8): 445-453]