Reference - Detail
|Author||Janssen T, Husson SJ, Lindemans M, Mertens I, Rademakers S, Ver Donck K, Geysen J, Jansen G, Schoofs L.|
|Title||Functional characterization of three G protein-coupled receptors for pigment dispersing factors in Caenorhabditis elegans.|
|Journal||J. Biol. Chem.|
Here, we report the identification, cloning, and functional characterization of three Caenorhabditis elegans G protein-coupled pigment dispersing factor (PDF) receptors, which we designated as Ce_PDFR-1a, -b, and -c. They represent three splice isoforms of the same gene (C13B9.4), which share a high degree of similarity with the Drosophila PDF receptor and are distantly related to the mammalian vasoactive intestinal peptide receptors (VPAC2) and calcitonin receptors. In a reverse pharmacological screen, three bioactive C. elegans neuropeptides, which were recently identified as the Drosophila PDF orthologues, were able to activate these receptors in a dose-dependent manner with nanomolar potency (isoforms a and b). Integrated green fluorescent protein reporter constructs reveal the expression of these PDF receptors in all body wall muscle cells and many head and tail neurons involved in the integration of environmental stimuli and the control of locomotion. Using a custom data analysis system, we demonstrate the involvement of this newly discovered neuropeptide signaling system in the regulation of locomotor behavior. Overexpression of PDF-2 phenocopies the locomotor defects of a PDF-1 null mutant, suggesting that they elicit opposite effects on locomotion through the identified PDF receptors. Our findings strengthen the hypothesis that the PDF signaling system, which imposes the circadian clock rhythm on behavior in Drosophila, has been functionally conserved throughout the protostomian evolutionary lineage.
|MeSH||Alternative Splicing / physiology* Amino Acid Sequence Animals Biological Evolution Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / biosynthesis* Caenorhabditis elegans Proteins / genetics Circadian Rhythm / physiology Dose-Response Relationship, Drug Drosophila Proteins / genetics Drosophila Proteins / metabolism Gene Expression Regulation / drug effects Gene Expression Regulation / physiology* Locomotion / physiology Mammals / genetics Mammals / metabolism Molecular Sequence Data Muscle Cells / metabolism Mutation Neurons / metabolism Neuropeptides / genetics Neuropeptides / metabolism Neuropeptides / pharmacology Organ Specificity / drug effects Organ Specificity / physiology Protein Isoforms / biosynthesis Protein Isoforms / genetics Receptors, Calcitonin / genetics Receptors, Calcitonin / metabolism Receptors, G-Protein-Coupled / biosynthesis* Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / metabolism Receptors, Vasoactive Intestinal Peptide, Type II / genetics Receptors, Vasoactive Intestinal Peptide, Type II / metabolism Sequence Homology, Amino Acid Signal Transduction / drug effects Signal Transduction / physiology*|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY|