Alleviating chronic ER stress by p38-Ire1-Xbp1 pathway and insulin-associated autophagy in C. elegans neurons

Autoři: Liying Guan aff001;  Zhigao Zhan aff001;  Yongzhi Yang aff001;  Yue Miao aff001;  Xun Huang aff001;  Mei Ding aff001
Působiště autorů: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China aff001;  University of Chinese Academy of Sciences, Beijing, China aff002
Vyšlo v časopise: Alleviating chronic ER stress by p38-Ire1-Xbp1 pathway and insulin-associated autophagy in C. elegans neurons. PLoS Genet 16(9): e32767. doi:10.1371/journal.pgen.1008704
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008704


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.

Klíčová slova:

Autophagic cell death – Caenorhabditis elegans – Cellular stress responses – Endoplasmic reticulum – Endoplasmic reticulum stress response – Neurons – Phosphorylation – Stress signaling cascade


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PLOS Genetics

2020 Číslo 9

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