Sanderson Thomas H, Gallaway Molly, Kumar Rita
Cardiovascular Research Institute and Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Int J Mol Sci. 2015 Mar 30;16(4):7133-42. doi: 10.3390/ijms16047133.
The endoplasmic reticulum (ER) is responsible for processing of proteins that are destined to be secreted, enclosed in a vesicle, or incorporated in the plasma membrane. Nascent peptides that enter the ER undergo a series of highly regulated processing steps to reach maturation as they transit the ER. Alterations in the intracellular environment that induce ER stress are thought to interrupt these processing steps, and result in unfolding of proteins in the ER. Accumulation of unfolded proteins concurrently activates three transmembrane stress sensors, IRE1, ATF6 and PERK, and is referred to as the Unfolded Protein Response (UPR). Our understanding of the mechanisms of UPR induction has been assembled primarily from experiments inducing ER stress with chemical and genetic manipulations. However, physiological stress often induces activation of ER stress sensors in a distinct manner from the canonical UPR. The unique activation profiles in vivo have prompted us to examine the mechanism of UPR activation in neurons following cerebral ischemia.
内质网（ER）负责处理那些注定要被分泌、包裹在囊泡中或整合到质膜中的蛋白质。进入内质网的新生肽在通过内质网时会经历一系列高度调控的加工步骤以达到成熟。诱导内质网应激的细胞内环境改变被认为会中断这些加工步骤，并导致内质网中的蛋白质解折叠。未折叠蛋白质的积累同时激活三种跨膜应激传感器，即肌醇需求酶1（IRE1）、活化转录因子6（ATF6）和蛋白激酶R样内质网激酶（PERK），这被称为未折叠蛋白反应（UPR）。我们对UPR诱导机制的理解主要来自于通过化学和基因操作诱导内质网应激的实验。然而，生理应激通常以与经典UPR不同的方式诱导内质网应激传感器的激活。体内独特的激活模式促使我们研究脑缺血后神经元中UPR激活的机制。
