Institute of Protein Biochemistry (IBP), Italian National Research Council (CNR), Napoli, Italy.
Institute of Protein Biochemistry (IBP), Italian National Research Council (CNR), Napoli, Italy.
Cell. 2019 Mar 7;176(6):1461-1476.e23. doi: 10.1016/j.cell.2019.01.035.
Maintaining the optimal performance of cell processes and organelles is the task of auto-regulatory systems. Here we describe an auto-regulatory device that helps to maintain homeostasis of the endoplasmic reticulum (ER) by adjusting the secretory flux to the cargo load. The cargo-recruiting subunit of the coatomer protein II (COPII) coat, Sec24, doubles as a sensor of folded cargo and, upon cargo binding, acts as a guanine nucleotide exchange factor to activate the signaling protein Gα12 at the ER exit sites (ERESs). This step, in turn, activates a complex signaling network that activates and coordinates the ER export machinery and attenuates proteins synthesis, thus preventing large fluctuations of folded and potentially active cargo that could be harmful to the cell or the organism. We call this mechanism AREX (autoregulation of ER export) and expect that its identification will aid our understanding of human physiology and diseases that develop from secretory dysfunction.
维持细胞过程和细胞器的最佳性能是自动调节系统的任务。在这里，我们描述了一种自动调节装置，它通过调节货物负载的分泌通量来帮助维持内质网 (ER) 的体内平衡。COPII 衣壳的货物募集亚基 Sec24 兼作折叠货物的传感器，并且在货物结合后，充当鸟嘌呤核苷酸交换因子，以激活内质网出口部位 (ERES) 的信号蛋白 Gα12。这一步反过来又激活了一个复杂的信号网络，该网络激活并协调 ER 输出机制，并减弱蛋白质合成，从而防止折叠和潜在活性货物的大幅波动，这可能对细胞或生物体有害。我们称这种机制为 AREX（内质网输出的自动调节），并期望它的鉴定将有助于我们理解人类生理学和由分泌功能障碍引起的疾病。
