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

Neuronal GPCR Controls Innate Immunity by Regulating Noncanonical Unfolded Protein Response Genes

Jingru Sun
, Varsha Singh
, Rie Kajino-Sakamoto
, Alejandro Aballay (Lead / Corresponding author)

Molecular Microbiology

Research output: Contribution to journal › Article › peer-review

218 Citations (Scopus)

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.

Original language	English
Pages (from-to)	729-732
Number of pages	4
Journal	Science
Volume	332
Issue number	6030
Early online date	7 Apr 2011
DOIs	https://doi.org/10.1126/science.1203411
Publication status	Published - 6 May 2011

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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General

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10.1126/science.1203411

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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.",

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Neuronal GPCR Controls Innate Immunity by Regulating Noncanonical Unfolded Protein Response Genes

Abstract

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