Inhibition of the oligosaccharyl transferase in Caenorhabditis elegans that compromises ER proteostasis suppresses p38-dependent protection against pathogenic bacteria


Autoři: Dae-Eun Jeong aff001;  Yujin Lee aff002;  Seokjin Ham aff002;  Dongyeop Lee aff001;  Sujeong Kwon aff002;  Hae-Eun H. Park aff002;  Sun-Young Hwang aff001;  Joo-Yeon Yoo aff001;  Tae-Young Roh aff001;  Seung-Jae V. Lee aff002
Působiště autorů: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea aff001;  Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Yuseong-Gu, Daejeon, South Korea aff002
Vyšlo v časopise: Inhibition of the oligosaccharyl transferase in Caenorhabditis elegans that compromises ER proteostasis suppresses p38-dependent protection against pathogenic bacteria. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008617
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008617

Souhrn

The oligosaccharyl transferase (OST) protein complex mediates the N-linked glycosylation of substrate proteins in the endoplasmic reticulum (ER), which regulates stability, activity, and localization of its substrates. Although many OST substrate proteins have been identified, the physiological role of the OST complex remains incompletely understood. Here we show that the OST complex in C. elegans is crucial for ER protein homeostasis and defense against infection with pathogenic bacteria Pseudomonas aeruginosa (PA14), via immune-regulatory PMK-1/p38 MAP kinase. We found that genetic inhibition of the OST complex impaired protein processing in the ER, which in turn up-regulated ER unfolded protein response (UPRER). We identified vitellogenin VIT-6 as an OST-dependent glycosylated protein, critical for maintaining survival on PA14. We also showed that the OST complex was required for up-regulation of PMK-1 signaling upon infection with PA14. Our study demonstrates that an evolutionarily conserved OST complex, crucial for ER homeostasis, regulates host defense mechanisms against pathogenic bacteria.

Klíčová slova:

Bacterial pathogens – Caenorhabditis elegans – DNA transcription – Endoplasmic reticulum – Gene expression – Immunity – RNA interference – Transcription factors


Zdroje

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Genetika Reprodukční medicína

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PLOS Genetics


2020 Číslo 3

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