Control of feeding behavior in C. elegans by human G protein-coupled receptors permits screening for agonist-expressing bacteria

M. S. Teng; P. Shadbolt; A. G. Fraser; G. Jansen; J. McCafferty

doi:10.1073/pnas.0803290105

Control of feeding behavior in C. elegans by human G protein-coupled receptors permits screening for agonist-expressing bacteria

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0803290105 ◽

2008 ◽

Vol 105 (39) ◽

pp. 14826-14831 ◽

Cited By ~ 2

Author(s):

M. S. Teng ◽

P. Shadbolt ◽

A. G. Fraser ◽

G. Jansen ◽

J. McCafferty

Keyword(s):

Feeding Behavior ◽

G Protein ◽

G Protein Coupled Receptors ◽

C Elegans ◽

G Protein Coupled

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Faculty Opinions recommendation of Control of feeding behavior in C. elegans by human G protein-coupled receptors permits screening for agonist-expressing bacteria.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1125840.582940 ◽

2008 ◽

Author(s):

Sachdev Sidhu ◽

Raffi Tonikian

Keyword(s):

Feeding Behavior ◽

G Protein ◽

G Protein Coupled Receptors ◽

C Elegans ◽

G Protein Coupled

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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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Identification of a Conserved, Orphan G Protein-Coupled Receptor Required for Efficient Pathogen Clearance in Caenorhabditis elegans

Infection and Immunity ◽

10.1128/iai.00034-19 ◽

2019 ◽

Vol 87 (4) ◽

Cited By ~ 2

Author(s):

Alexandra Anderson ◽

Yee Lian Chew ◽

William Schafer ◽

Rachel McMullan

Keyword(s):

Caenorhabditis Elegans ◽

Immune Responses ◽

G Protein ◽

G Protein Coupled Receptors ◽

G Protein Coupled Receptor ◽

Content Type ◽

C Elegans ◽

Host Immune Responses ◽

Pathogen Clearance ◽

G Protein Coupled

ABSTRACT G protein-coupled receptors contribute to host defense across the animal kingdom, transducing many signals involved in both vertebrate and invertebrate immune responses. While it has become well established that the nematode worm Caenorhabditis elegans triggers innate immune responses following infection with numerous bacterial, fungal, and viral pathogens, the mechanisms by which C. elegans recognizes these pathogens have remained somewhat more elusive. C. elegans G protein-coupled receptors have been implicated in recognizing pathogen-associated damage and activating downstream host immune responses. Here we identify and characterize a novel G protein-coupled receptor required to regulate the C. elegans response to infection with Microbacterium nematophilum. We show that this receptor, which we designate pathogen clearance-defective receptor 1 (PCDR-1), is required for efficient pathogen clearance following infection. PCDR-1 acts upstream of multiple G proteins, including the C. elegans Gαq ortholog, EGL-30, in rectal epithelial cells to promote pathogen clearance via a novel mechanism.

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Binding site identification of G protein-coupled receptors through a 3D Zernike polynomials-based method: application to C. elegans olfactory receptors

Journal of Computer-Aided Molecular Design ◽

10.1007/s10822-021-00434-1 ◽

2022 ◽

Author(s):

Lorenzo Di Rienzo ◽

Luca De Flaviis ◽

Giancarlo Ruocco ◽

Viola Folli ◽

Edoardo Milanetti

Keyword(s):

Binding Site ◽

G Protein ◽

Molecular Mechanisms ◽

Model Organism ◽

Olfactory Receptors ◽

G Protein Coupled Receptors ◽

Zernike Polynomials ◽

C Elegans ◽

Shape Complementarity ◽

G Protein Coupled

AbstractStudying the binding processes of G protein-coupled receptors (GPCRs) proteins is of particular interest both to better understand the molecular mechanisms that regulate the signaling between the extracellular and intracellular environment and for drug design purposes. In this study, we propose a new computational approach for the identification of the binding site for a specific ligand on a GPCR. The method is based on the Zernike polynomials and performs the ligand-GPCR association through a shape complementarity analysis of the local molecular surfaces. The method is parameter-free and it can distinguish, working on hundreds of experimentally GPCR-ligand complexes, binding pockets from randomly sampled regions on the receptor surface, obtaining an Area Under ROC curve of 0.77. Given its importance both as a model organism and in terms of applications, we thus investigated the olfactory receptors of the C. elegans, building a list of associations between 21 GPCRs belonging to its olfactory neurons and a set of possible ligands. Thus, we can not only carry out rapid and efficient screenings of drugs proposed for GPCRs, key targets in many pathologies, but also we laid the groundwork for computational mutagenesis processes, aimed at increasing or decreasing the binding affinity between ligands and receptors.

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