Organismal regulation of XBP-1-mediated unfolded protein response during development and immune activation.
The increased demand on protein folding in the endoplasmic reticulum (ER) during bacterial infection activates the unfolded protein response (UPR). OCTR-1--a G protein-coupled catecholamine receptor expressed in neurons--suppresses innate immunity by downregulating a non-canonical UPR pathway and the p38 MAPK pathway. Here, we show that OCTR-1 also regulates the canonical UPR pathway, which is controlled by XBP-1, at the organismal level. Importantly, XBP-1 is not under OCTR-1 control during development, only at the adult stage. Our results indicate that the nervous system temporally controls the UPR pathway to maintain ER homeostasis during development and immune activation.
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Jingru
J
Sun
Yiyong
Y
Liu
Alejandro
A
Aballay
D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007113:Immunity, Innate; D009474:Neurons / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D056811:Unfolded Protein Response
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C558250:OCTR-1 protein, C elegans; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; C548541:XBP-1 protein, C elegans