Title
Functional characterization of three G protein-coupled receptors for pigment dispersing factors in **Caenorhabditis elegans** Functional characterization of three G protein-coupled receptors for pigment dispersing factors in **Caenorhabditis elegans**
Author
Faculty/Department
Faculty of Sciences. Biology
Faculty of Sciences. Chemistry
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Baltimore, Md ,
Subject
Chemistry
Biology
Source (journal)
Journal of biological chemistry. - Baltimore, Md
Volume/pages
283(2008) :22 , p. 15241-15249
ISSN
0021-9258
ISI
000256232000042
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
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.
E-info
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