Inhibition of the Oligosaccharyl Transferase in Caenorhabditis Elegans That Compromises ER Proteostasis Suppresses p38-dependent Protection Against Pathogenic Bacteria

PLoS Genet. 2020 Mar 4;16(3):e1008617. doi: 10.1371/journal.pgen.1008617. eCollection 2020 Mar.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Hexosyltransferases / metabolism
  • Immunity, Innate / physiology
  • MAP Kinase Signaling System / physiology
  • Membrane Proteins / metabolism
  • Proteostasis / physiology*
  • Pseudomonas aeruginosa / metabolism
  • Signal Transduction / physiology
  • Transcription Factors / metabolism
  • Unfolded Protein Response / physiology
  • Up-Regulation / physiology
  • Vitellogenins / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Membrane Proteins
  • Transcription Factors
  • VIT-6 protein, C elegans
  • Vitellogenins
  • Hexosyltransferases
  • dolichyl-diphosphooligosaccharide - protein glycotransferase
  • p38 Mitogen-Activated Protein Kinases

Grant support

This research was supported by grants NRF-2016R1E1A1A01941152 and NRF-2017R1A5A1015366 funded by the Ministry of Education, Science and Technology through the National Research Foundation (NRF) of Korea to S-JVL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.