Open AccessAlleviating chronic ER stress by p38-Ire1-Xbp1 pathway and insulin-associated autophagy in C. elegans neurons
Author(s) -
Lina Guan,
Zhigao Zhan,
Yongzhi Yang,
Yue Miao,
Xun Huang,
Mei Ding
Publication year - 2020
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1008704
Subject(s) - unfolded protein response , autophagy , xbp1 , biology , microbiology and biotechnology , p38 mitogen activated protein kinases , transcription factor , signal transduction , integrated stress response , stress granule , endoplasmic reticulum , downregulation and upregulation , mapk/erk pathway , gene , apoptosis , genetics , translation (biology) , rna , rna splicing , messenger rna
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.