Department of Biology and the Center for Cell and Genome Science, University of Utah, Salt Lake City, Utah 84112-0840, USA.
Annu Rev Genet. 2012;46:165-83. doi: 10.1146/annurev-genet-110711-155644. Epub 2012 Aug 28.
The endoplasmic reticulum (ER) controls many important aspects of cellular function, including processing of secreted and membrane proteins, synthesis of membranes, and calcium storage. Maintenance of ER function is controlled through a network of signaling pathways collectively known as the unfolded protein response (UPR). The UPR balances the load of incoming proteins with the folding capacity of the ER and allows cells to adapt to situations that disrupt this balance. This disruption is referred to as ER stress. Although ER stress often arises in pathological situations, the UPR plays a central role in the normal development and function of cells specializing in secretion. Many aspects of this response are conserved broadly across eukaryotes; most organisms use some subset of a group of ER transmembrane proteins to signal to the nucleus and induce a broad transcriptional upregulation of genes involved in ER function. However, new developments in metazoans, plants, and fungi illustrate interesting variations on this theme. Here, we summarize mechanisms for detecting and counteracting ER stress, the role of the UPR in normal secretory cell function, and how these pathways vary across organisms and among different tissues and cell types.
内质网（ER）控制着细胞功能的许多重要方面，包括分泌蛋白和膜蛋白的加工、膜的合成和钙的储存。内质网功能的维持是通过一个被称为未折叠蛋白反应（UPR）的信号通路网络来控制的。UPR 平衡了内质网的折叠能力与输入蛋白质的负荷，并允许细胞适应破坏这种平衡的情况。这种破坏被称为内质网应激。虽然内质网应激通常出现在病理情况下，但 UPR 在专门分泌的细胞的正常发育和功能中起着核心作用。这种反应的许多方面在真核生物中广泛保守；大多数生物体使用一组内质网跨膜蛋白的子集向细胞核发出信号，并诱导与 ER 功能相关的基因的广泛转录上调。然而，后生动物、植物和真菌的新发展说明了这个主题的有趣变化。在这里，我们总结了检测和对抗内质网应激的机制、UPR 在正常分泌细胞功能中的作用，以及这些途径在不同生物体和不同组织和细胞类型中的差异。
