RRC ID 12697
Author Richardson CE, Kinkel S, Kim DH.
Title Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabditis elegans larval development and immunity.
Journal PLoS Genet.
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.
Volume 7(11)
Pages e1002391
Published 2011-11
DOI 10.1371/journal.pgen.1002391
PMID 22125500
PMC PMC3219621
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans / immunology* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Carrier Proteins / genetics* Carrier Proteins / metabolism Cell Cycle Proteins / genetics* Cell Cycle Proteins / metabolism Endoplasmic Reticulum Stress / drug effects Endoplasmic Reticulum Stress / genetics Feedback, Physiological Gene Expression Regulation, Developmental Homeostasis / genetics Homeostasis / physiology Immunity / genetics* Larva / genetics Larva / growth & development MAP Kinase Kinase 1 / genetics* MAP Kinase Kinase 1 / metabolism Mutant Proteins / genetics Mutant Proteins / metabolism Protein-Serine-Threonine Kinases / genetics* Protein-Serine-Threonine Kinases / metabolism Signal Transduction Temperature Tunicamycin / pharmacology Unfolded Protein Response / genetics Unfolded Protein Response / physiology
IF 5.54
Times Cited 26
C.elegans tm2482 tm629