Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes

Jingru Sun; Varsha Singh; Rie Kajino-Sakamoto; Alejandro Aballay

doi:10.1126/science.1203411

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Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes

Journal article

Open access

Peer reviewed

Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes

Jingru Sun, Varsha Singh, Rie Kajino-Sakamoto and Alejandro Aballay

Science (American Association for the Advancement of Science), Vol.332(6030), pp.729-732

05/06/2011

DOI: https://doi.org/10.1126/science.1203411

Handle:

https://hdl.handle.net/2376/108933

PMID: 21474712

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Abstract

Pseudomonas aeruginosa - immunology

Caenorhabditis elegans - microbiology

Up-Regulation

Genes, Helminth

Stress, Physiological

Caenorhabditis elegans Proteins - metabolism

Endoplasmic Reticulum - metabolism

Intestines - metabolism

Pseudomonas aeruginosa - pathogenicity

Sensory Receptor Cells - physiology

Transcription, Genetic

Membrane Proteins - metabolism

Receptors, G-Protein-Coupled - physiology

Signal Transduction

Unfolded Protein Response - genetics

Caenorhabditis elegans - genetics

Membrane Proteins - genetics

Down-Regulation

Pharynx - metabolism

Bacterial Load

Immunity, Innate

Caenorhabditis elegans - immunology

Animals

Mitogen-Activated Protein Kinases - genetics

Caenorhabditis elegans Proteins - physiology

Receptors, G-Protein-Coupled - genetics

Mutation

Caenorhabditis elegans Proteins - genetics

Mitogen-Activated Protein Kinases - metabolism

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.

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Title: Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes
Creators: Jingru Sun - Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27705, USA
Varsha Singh
Rie Kajino-Sakamoto
Alejandro Aballay
Publication Details: Science (American Association for the Advancement of Science), Vol.332(6030), pp.729-732
Academic Unit: Biomedical Sciences, Department of
Publisher: United States
Grant note: R01 GM070977 / NIGMS NIH HHS GM070977 / NIGMS NIH HHS
Identifiers: 99900547386601842
Language: English
Resource Type: Journal article