Dynamic retention of Ero1α and Er1β in the endoplasmic reticulum by interactions with PDI and ERp44
Dynamic retention of Ero1α and Er1β in the endoplasmic reticulum by interactions with PDI and ERp44
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DOI：
10.1089/ars.2006.8.274
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发表时间：
2006-03-01
影响因子：
6.6
通讯作者：
Sitia, Roberto
中科院分区：
文献类型：
--
作者：
Otsu, Mieko;Bertoli, Gloria;Sitia, Roberto
二硫键在内质网（ER）中通过顺序交换反应形成：Ero 1 α和Ero 1 β将氧化等价物转移到蛋白质二硫键异构酶（PDI），后者反过来氧化货物蛋白。Ero 1 alpha和Ero 1 beta都不包含已知的ER定位基序，这就提出了它们如何保留在这个细胞器中的问题。在这里，作者表明，与内源性分子不同，过表达的Erolot和Ero 1 β由HeLa转染子分泌，表明其正常保留机制饱和。PDI或ERp 44的共表达以KDEL/RDEL依赖性方式阻止Ero 1分泌。ERp 44和Ero 1之间的共价相互作用对于保留是必不可少的。相比之下，在两个活性位点中缺乏四个半胱氨酸的突变体PDI仍然抑制分泌，尽管效率较低。PRI和ERp 44竞争Ero 1结合。PDI还阻止Ero 1聚集和二聚化，从而陪伴其自身的氧化酶。Ero 1的这种动态保留机制可能对ER氧化还原稳态的调节和质量控制具有重要意义。
Disulfide bonds are formed in the endoplasmic reticulum (ER) by sequential interchange reactions: Ero1 alpha and Ero1 beta transfer oxidative equivalents to protein disulfide isomerase (PDI), which in turn oxidizes cargo proteins. Neither Ero1 alpha nor Ero1 beta contains known ER localization motif(s), raising the question of how they are retained in this organelle. Here the authors show that, unlike endogenous molecules, overexpressed Erolot and Ero1 beta are secreted by HeLa transfectants, suggesting saturation of their normal retention mechanism(s). Co-expression of either PDI or ERp44 prevents Ero1 secretion in a KDEL/RDEL dependent way. Covalent interactions between ERp44 and Ero1 are essential for retention. In contrast, a mutant PDI lacking the four cysteines in the two active sites still inhibits secretion, albeit less efficiently. PRI and ERp44 compete for Ero1 binding. PDI also prevents Ero1 aggregation and dimerization, thus chaperoning its own oxidase. This dynamic retention mechanism of Ero1 may be important for fine-tuning the regulation of ER redox homeostasis and quality control.