title: Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabditis elegans larval development and immunity.
abstract: Endoplasmic reticulum (ER) stress activates the Unfolded Protein Response, a compensatory signaling response that is mediated by the IRE-1, PERK/PEK-1, and ATF-6 pathways in metazoans. Genetic studies have implicated roles for UPR signaling in animal development and disease, but the function of the UPR under physiological conditions, in the absence of chemical agents administered to induce ER stress, is not well understood. Here, we show that in Caenorhabditis elegans XBP-1 deficiency results in constitutive ER stress, reflected by increased basal levels of IRE-1 and PEK-1 activity under physiological conditions. We define a dynamic, temperature-dependent requirement for XBP-1 and PEK-1 activities that increases with immune activation and at elevated physiological temperatures in C. elegans. Our data suggest that the negative feedback loops involving the activation of IRE-1-XBP-1 and PEK-1 pathways serve essential roles, not only at the extremes of ER stress, but also in the maintenance of ER homeostasis under physiological conditions.
authors: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Claire E
authors: CE
authors: Richardson
authors: Stephanie
authors: S
authors: Kinkel
authors: Dennis H
authors: DH
authors: Kim
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D007109:Immunity / Q000235:genetics*; D007814:Larva / Q000235:genetics / Q000254:growth & development; D048369:MAP Kinase Kinase 1 / Q000235:genetics* / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013696:Temperature; D014415:Tunicamycin / Q000494:pharmacology; D056811:Unfolded Protein Response / Q000235:genetics / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050505:Mutant Proteins; C548541:XBP-1 protein, C elegans; D014415:Tunicamycin; D017346:Protein Serine-Threonine Kinases; C499574:pek-1 protein, C elegans; C541905:IRE-1 protein, C elegans; D048369:MAP Kinase Kinase 1