title: Functional characterization of three G protein-coupled receptors for pigment dispersing factors in Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Functional Genomics and Proteomics Unit, Department of Biology, K.U. Leuven, Naamsestraat 59, Leuven, Belgium. Tom.Janssen@bio.kuleuven.be
authors.forename: Tom
authors.initials: T
authors.lastname: Janssen
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Husson
authors.forename: Marleen
authors.initials: M
authors.lastname: Lindemans
authors.forename: Inge
authors.initials: I
authors.lastname: Mertens
authors.forename: Suzanne
authors.initials: S
authors.lastname: Rademakers
authors.forename: Kris
authors.initials: K
authors.lastname: Ver Donck
authors.forename: Johan
authors.initials: J
authors.lastname: Geysen
authors.forename: Gert
authors.initials: G
authors.lastname: Jansen
authors.forename: Liliane
authors.initials: L
authors.lastname: Schoofs
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis* / Q000235:genetics; D002940:Circadian Rhythm / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008124:Locomotion / Q000502:physiology; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D009928:Organ Specificity / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D018003:Receptors, Calcitonin / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D009479:Neuropeptides; C507073:PDFR protein, Drosophila; C530057:PDFR-1 protein, C elegans; D020033:Protein Isoforms; D018003:Receptors, Calcitonin; D043562:Receptors, G-Protein-Coupled; D051239:Receptors, Vasoactive Intestinal Peptide, Type II