State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
PLoS Genet. 2020 Sep 28;16(9):e1008704. doi: 10.1371/journal.pgen.1008704. eCollection 2020 Sep.
ER stress occurs in many physiological and pathological conditions. However, how chronic ER stress is alleviated in specific cells in an intact organism is an outstanding question. Here, overexpressing the gap junction protein UNC-9 (Uncoordinated) in C. elegans neurons triggers the Ire1-Xbp1-mediated stress response in an age-dependent and cell-autonomous manner. The p38 MAPK PMK-3 regulates the chronic stress through IRE-1 phosphorylation. Overexpressing gap junction protein also activates autophagy. The insulin pathway functions through autophagy, but not the transcription of genes encoding ER chaperones, to counteract the p38-Ire1-Xbp1-mediated stress response. Together, these results reveal an intricate cellular regulatory network in response to chronic stress in a subset of cells in multicellular organism.
内质网应激发生在许多生理和病理条件下。然而，在完整生物体中，慢性内质网应激如何在特定细胞中得到缓解，仍是一个悬而未决的问题。在这里，在秀丽隐杆线虫的神经元中过表达间隙连接蛋白 UNC-9（Uncoordinated）会以年龄依赖和细胞自主的方式触发 Ire1-Xbp1 介导的应激反应。p38 MAPK PMK-3 通过 IRE-1 磷酸化来调节慢性应激。过表达间隙连接蛋白也会激活自噬。胰岛素途径通过自噬而不是通过编码内质网伴侣的基因的转录来发挥作用，以对抗 p38-Ire1-Xbp1 介导的应激反应。总之，这些结果揭示了在多细胞生物的一部分细胞中，对慢性应激的复杂细胞调控网络。
