Neural G protein-coupled receptor OCTR-1 mediates temperature effects on longevity by regulating immune response genes in C. elegans

We have previously demonstrated that OCTR-1, an octopamine G protein-couple receptor, functions in the sensory neurons ASH to suppress the innate immune response in Caenorhabditis elegans by inhibiting the expression of immune genes (Sun et al. 2011 Science 332:729-732). Here we discover that OCTR-1 also regulates temperature effects on lifespan in C. elegans. At the normal growth temperature 20⁰C, octr-1(ok371) mutant animals have similar lifespan to wild-type N2 animals. However, at higher temperature 25⁰C, octr-1(ok371) mutants live significant longer than wild-type N2 animals. These results suggest that OCTR-1 may mediate temperature effects on lifespan. Furthermore, we found the OCTR-1-expressing ASH chemosensory neurons are involved in the OCTR-1-mediated regulation on longevity. However, interestingly, the thermosensory AFD neurons do not play a role in this regulation at 25⁰C. RNA-seq data analysis showed that 63 immune response genes were significantly down-regulated in octr-1(ok371) mutants relative to wild-type animals at 25⁰C. We further demonstrated that inactivation of several most-downregulated genes by RNA interference in wild-type N2 animals significantly extended their lifespan, similar to the phenotype of octr-1(ok371) animals. These observations suggest a new molecular regulation mechanism that downregulation of immune genes extends the lifespan of C. elegans, which is opposite to the general belief that an increase in defense immunity extends lifespan.

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Isolation, characterization and epistasis of fluoride-resistant mutants of Caenorhabditis elegans.

Genetics ◽

10.1093/genetics/136.1.145 ◽

1994 ◽

Vol 136 (1) ◽

pp. 145-154

Author(s):

I Katsura ◽

K Kondo ◽

T Amano ◽

T Ishihara ◽

M Kawakami

Keyword(s):

Caenorhabditis Elegans ◽

Brood Size ◽

Normal Growth ◽

Fluoride Ion ◽

Wild Type ◽

Signal Transduction System ◽

Nematode Caenorhabditis Elegans ◽

C Elegans ◽

Class 1 ◽

Resistant Mutants

Abstract We have isolated 13 fluoride-resistant mutants of the nematode Caenorhabditis elegans. All the mutations are recessive and mapped to five genes. Mutants in three of the genes (class 1 genes: flr-1 X, flr-3 IV, and flr-4 X) are resistant to 400 micrograms/ml NaF. Furthermore, they grow twice as slowly as and have smaller brood size than wild-type worms even in the absence of fluoride ion. In contrast, mutants in the other two genes (class 2 genes: flr-2 V and flr-5 V) are only partially resistant to 400 micrograms/ml NaF, and they have almost normal growth rates and brood sizes in the absence of fluoride ion. Studies on the phenotypes of double mutants showed that class 2 mutations are epistatic to class 1 mutations concerning growth rate and brood size but hypostatic with respect to fluoride resistance. We propose two models that can explain the epistasis. Since fluoride ion depletes calcium ion, inhibits some protein phosphatases and activates trimeric G-proteins, studies on these mutants may lead to discovery of a new signal transduction system that controls the growth of C. elegans.

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Melatonin promotes sleep by activating the BK channel in C. elegans

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2010928117 ◽

2020 ◽

Vol 117 (40) ◽

pp. 25128-25137

Author(s):

Longgang Niu ◽

Yan Li ◽

Pengyu Zong ◽

Ping Liu ◽

Yuan Shui ◽

...

Keyword(s):

G Protein ◽

Neurotransmitter Release ◽

Expression System ◽

Molecular Target ◽

Bk Channel ◽

G Protein Coupled Receptors ◽

Wild Type ◽

Heterologous Expression System ◽

C Elegans ◽

G Protein Coupled

Melatonin (Mel) promotes sleep through G protein-coupled receptors. However, the downstream molecular target(s) is unknown. We identified the Caenorhabditis elegans BK channel SLO-1 as a molecular target of the Mel receptor PCDR-1-. Knockout of pcdr-1, slo-1, or homt-1 (a gene required for Mel synthesis) causes substantially increased neurotransmitter release and shortened sleep duration, and these effects are nonadditive in double knockouts. Exogenous Mel inhibits neurotransmitter release and promotes sleep in wild-type (WT) but not pcdr-1 and slo-1 mutants. In a heterologous expression system, Mel activates the human BK channel (hSlo1) in a membrane-delimited manner in the presence of the Mel receptor MT1 but not MT2. A peptide acting to release free Gβγ also activates hSlo1 in a MT1-dependent and membrane-delimited manner, whereas a Gβλ inhibitor abolishes the stimulating effect of Mel. Our results suggest that Mel promotes sleep by activating the BK channel through a specific Mel receptor and Gβλ.

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