Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
EMBO Rep. 2012 Sep;13(9):855-60. doi: 10.1038/embor.2012.100. Epub 2012 Jul 13.
The increased demand on protein folding in the endoplasmic reticulum (ER) during bacterial infection activates the unfolded protein response (UPR). OCTR-1--a G protein-coupled catecholamine receptor expressed in neurons--suppresses innate immunity by downregulating a non-canonical UPR pathway and the p38 MAPK pathway. Here, we show that OCTR-1 also regulates the canonical UPR pathway, which is controlled by XBP-1, at the organismal level. Importantly, XBP-1 is not under OCTR-1 control during development, only at the adult stage. Our results indicate that the nervous system temporally controls the UPR pathway to maintain ER homeostasis during development and immune activation.
在细菌感染过程中，内质网（ER）中蛋白质折叠的需求增加会激活未折叠蛋白反应（UPR）。OCTR-1——一种在神经元中表达的 G 蛋白偶联儿茶酚胺受体——通过下调非典型 UPR 途径和 p38 MAPK 途径来抑制先天免疫。在这里，我们表明 OCTR-1 还在机体水平上调节由 XBP-1 控制的经典 UPR 途径。重要的是，XBP-1 在发育过程中不受 OCTR-1 的控制，仅在成年期受其控制。我们的结果表明，神经系统在发育和免疫激活过程中通过时间控制 UPR 途径来维持 ER 内稳态。
