Coat protein complex II (COPII) plays an essential role in the export of cargo molecules such as secretory proteins, membrane proteins, and lipids from the endoplasmic reticulum (ER). In yeast, the COPII machinery is critical for cell viability as most COPII knockout mutants fail to survive. In mice and fish, homozygous knockout mutants of most COPII genes are embryonic lethal, reflecting the essentiality of the COPII machinery in the early stages of vertebrate development. In humans, COPII mutations, which are often hypomorphic, cause diseases having distinct clinical features. This is interesting as the fundamental cellular defect of these diseases, that is, failure of ER export, is similar. Analyses of humans and animals carrying COPII mutations have revealed clues to why a similar ER export defect can cause such different diseases. Previous reviews have focused mainly on the deficit of secretory or membrane proteins in the final destinations because of an ER export block. In this review, we also underscore the other consequence of the ER export block, namely ER stress triggered by the accumulation of cargo proteins in the ER.

中文翻译：

---

脊椎动物内质网输出机制 COPII 基因突变的后果。


外壳蛋白复合物 II (COPII) 在货物分子（例如分泌蛋白、膜蛋白和内质网 (ER) 脂质）的输出中发挥着重要作用。在酵母中，COPII 机制对于细胞活力至关重要，因为大多数 COPII 敲除突变体无法存活。在小鼠和鱼类中，大多数 COPII 基因的纯合敲除突变体是胚胎致死的，这反映了 COPII 机制在脊椎动物发育早期阶段的重要性。在人类中，COPII 突变通常是低效的，会导致具有独特临床特征的疾病。这很有趣，因为这些疾病的基本细胞缺陷，即 ER 输出失败，是相似的。对携带 COPII 突变的人类和动物的分析揭示了为什么类似的 ER 输出缺陷会导致如此不同的疾病的线索。之前的审查主要集中在由于内质网出口受阻而导致最终目的地的分泌蛋白或膜蛋白的缺乏。在这篇综述中，我们还强调了内质网输出阻断的另一个后果，即内质网中货物蛋白积累引发的内质网应激。