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author:(Liliane J dable)
1.  Neuropeptide GPCRs in C. elegans 
Like most organisms, the nematode Caenorhabditis elegans relies heavily on neuropeptidergic signaling. This tiny animal represents a suitable model system to study neuropeptidergic signaling networks with single cell resolution due to the availability of powerful molecular and genetic tools. The availability of the worm’s complete genome sequence allows researchers to browse through it, uncovering putative neuropeptides and their cognate G protein-coupled receptors (GPCRs). Many predictions have been made about the number of C. elegans neuropeptide GPCRs. In this review, we report the state of the art of both verified as well as predicted C. elegans neuropeptide GPCRs. The predicted neuropeptide GPCRs are incorporated into the receptor classification system based on their resemblance to orthologous GPCRs in insects and vertebrates. Appointing the natural ligand(s) to each predicted neuropeptide GPCR (receptor deorphanization) is a crucial step during characterization. The development of deorphanization strategies resulted in a significant increase in the knowledge of neuropeptidergic signaling in C. elegans. Complementary localization and functional studies demonstrate that neuropeptides and their GPCRs represent a rich potential source of behavioral variability in C. elegans. Here, we review all neuropeptidergic signaling pathways that so far have been functionally characterized in C. elegans.
doi:10.3389/fendo.2012.00167
PMCID: PMC3527849  PMID: 23267347
nematoda; Caenorhabditis elegans; G protein-coupled receptor; neuropeptidergic signaling; GPCR deorphanization
2.  UNC-108/RAB-2 and its effector RIC-19 are involved in dense core vesicle maturation in Caenorhabditis elegans 
The Journal of Cell Biology  2009;186(6):897-914.
Uncoordinated movement in Rab2 mutants is caused by impaired retention of cargo on dense core vesicles, not by defective synaptic vesicle release. (Also see the companion article by Edwards et al. in this issue.)
Small guanosine triphosphatases of the Rab family regulate intracellular vesicular trafficking. Rab2 is highly expressed in the nervous system, yet its function in neurons is unknown. In Caenorhabditis elegans, unc-108/rab-2 mutants have been isolated based on their locomotory defects. We show that the locomotion defects of rab-2 mutants are not caused by defects in synaptic vesicle release but by defects in dense core vesicle (DCV) signaling. DCVs in rab-2 mutants are often enlarged and heterogeneous in size; however, their number and distribution are not affected. This implicates Rab2 in the biogenesis of DCVs at the Golgi complex. We demonstrate that Rab2 is required to prevent DCV cargo from inappropriately entering late endosomal compartments during DCV maturation. Finally, we show that RIC-19, the C. elegans orthologue of the human diabetes autoantigen ICA69, is also involved in DCV maturation and is recruited to Golgi membranes by activated RAB-2. Thus, we propose that RAB-2 and its effector RIC-19 are required for neuronal DCV maturation.
doi:10.1083/jcb.200902096
PMCID: PMC2753160  PMID: 19797081
3.  Functional Characterization of Three G Protein-coupled Receptors for Pigment Dispersing Factors in Caenorhabditis elegans*S⃞ 
The Journal of Biological Chemistry  2008;283(22):15241-15249.
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.
doi:10.1074/jbc.M709060200
PMCID: PMC3258896  PMID: 18390545

Results 1-3 (3)