title: Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes.
abstract: The unfolded protein response (UPR), which is activated when unfolded or misfolded proteins accumulate in the endoplasmic reticulum, has been implicated in the normal physiology of immune defense and in several human diseases, including diabetes, cancer, neurodegenerative disease, and inflammatory disease. In this study, we found that the nervous system controlled the activity of a noncanonical UPR pathway required for innate immunity in Caenorhabditis elegans. OCTR-1, a putative octopamine G protein-coupled catecholamine receptor (GPCR, G protein-coupled receptor), functioned in sensory neurons designated ASH and ASI to actively suppress innate immune responses by down-regulating the expression of noncanonical UPR genes pqn/abu in nonneuronal tissues. Our findings suggest a molecular mechanism by which the nervous system may sense inflammatory responses and respond by controlling stress-response pathways at the organismal level.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Jingru
authors.initials: J
authors.lastname: Sun
authors.forename: Varsha
authors.initials: V
authors.lastname: Singh
authors.forename: Rie
authors.initials: R
authors.lastname: Kajino-Sakamoto
authors.forename: Alejandro
authors.initials: A
authors.lastname: Aballay
mesh_terms: D000818:Animals; D058491:Bacterial Load; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017238:Genes, Helminth; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010614:Pharynx / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000502:physiology*; D015398:Signal Transduction; D013312:Stress, Physiological; D014158:Transcription, Genetic; D056811:Unfolded Protein Response / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; C558250:OCTR-1 protein, C elegans; D043562:Receptors, G-Protein-Coupled; C422043:ced-1 protein, C elegans; D020928:Mitogen-Activated Protein Kinases; C463460:Pmk-1 protein, C elegans