Select Neuropeptides and their G-Protein Coupled Receptors in Caenorhabditis Elegans and Drosophila Melanogaster

Bendena, William G.; Campbell, Jason C.; Zara, Lian C.; Tobe, Stephen S.; Chin-Sang, Ian D.

doi:10.3389/fendo.2012.00093

Cited by 17 publications

(8 citation statements)

References 118 publications

(143 reference statements)

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“…However, loss of flp-21 only slightly increases aggregation in animals bearing the Val-215 allele, suggesting that another ligand most likely encoded by the flp-18 gene may functionally substitute for the loss of FLP-21 ligands ( 61 , 95 ). FLP-21 furthermore does not appear to act in NPR-1 dependent acute ethanol tolerance, once again suggesting that FLP-18 may be a physiological active ligand ( 97 ).…”

Section: Flp-mediated Modulation Of Nematode Physiology and Behaviormentioning

confidence: 99%

The FMRFamide-Like Peptide Family in Nematodes

et al. 2014

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In the three decades since the FMRFamide peptide was isolated from the mollusk Macrocallista nimbosa, structurally similar peptides sharing a C-terminal RFamide motif have been identified across the animal kingdom. FMRFamide-like peptides (FLPs) represent the largest known family of neuropeptides in invertebrates. In the phylum Nematoda, at least 32 flp-genes are classified, making the FLP system of nematodes unusually complex. The diversity of the nematode FLP complement is most extensively mapped in Caenorhabditis elegans, where over 70 FLPs have been predicted. FLPs have shown to be expressed in the majority of the 302 C. elegans neurons including interneurons, sensory neurons, and motor neurons. The vast expression of FLPs is reflected in the broad functional repertoire of nematode FLP signaling, including neuroendocrine and neuromodulatory effects on locomotory activity, reproduction, feeding, and behavior. In contrast to the many identified nematode FLPs, only few peptides have been assigned a receptor and there is the need to clarify the pathway components and working mechanisms of the FLP signaling network. Here, we review the diversity, distribution, and functions of FLPs in nematodes.

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Section: Flp-mediated Modulation Of Nematode Physiology and Behaviormentioning

confidence: 99%

The FMRFamide-Like Peptide Family in Nematodes

et al. 2014

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“…These findings demonstrate that they can serve as models to gain insights into the biology and molecular mechanisms of the respective other system. While several other organisms have been successfully employed to investigate functions of neuropeptides and their receptors such as Drosophila melanogaster (summarized in [10]), with the knowledge of our study on hand, the nematode offers distinct advantages for more generic studies. For instance, its transparency enables tracking of multiple fluorescently labeled peptides and monitoring their dynamics.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological and functional similarities of the human neuropeptide Y system in C. elegans challenges phylogenetic views on the FLP/NPR system

et al. 2019

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Background The neuropeptide Y system affects various processes, among others food intake, and is frequently discussed in the context of targeting obesity. Studies in model organisms are indispensable to enable molecular studies in a physiological context. Although the NPY system is evolutionarily conserved in all bilaterians, in the widely used model Caenorhabditis elegans there is controversy on the existence of NPY orthologous molecules. While the FMRFamide-like peptide (FLP)/Neuropeptide receptor-Resemblance (NPR) system in the nematode was initially suggested to be orthologous to the mammalian NPY system, later global phylogenetic studies indicate that FLP/NPR is protostome-specific. Methods We performed a comprehensive pharmacological study of the FLP/NPR system in transfected cells in vitro, and tested for functional substitution in C. elegans knockout strains. Further, we phenotypically compared different flp loss-of-function strains. Differences between groups were compared by ANOVA and post-hoc testing (Dunnett, Bonferroni). Results Our pharmacological analysis of the FLP/NPR system including formerly functionally uncharacterized NPY-like peptides from C. elegans demonstrates that G protein-coupling and ligand requirements for receptor activation are similar to the human NPY system. In vitro and in vivo analyses show cross-reactivity of NPY with the FLP/NPR system manifesting in the ability of the human GPCRs to functionally substitute FLP/NPR signaling in vivo. The high pharmacological/functional similarities enabled us to identify C. elegans FLP-14 as a key molecule in avoidance behavior. Conclusions Our data demonstrate the pharmacological and functional similarities of human NPY and C. elegans NPR systems. This adds a novel perspective to current phylogenetic reconstructions of the neuropeptide Y system. NPY and NPR receptors are pharmacologically so similar that the human receptors can functionally compensate for the C. elegans ones, suggesting orthologous relationships. This is also underlined by the presence of NPY-like peptides and parallels in peptide requirements for receptor activation. Further, the results presented here highlight the potential of this knowledge for physiological as well as molecular studies on neuropeptide GPCRs such as the NPY system in the future.

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“…The use of heterologous expression systems, however, prevents that compounds present in an insect extract, or predicted insect ligands would activate endogenous mammalian or amphibian receptors (for reviews, see: Meeusen et al, 2003; Mertens et al, 2004; Beets et al, 2011; Bendena et al, 2012). …”

Section: Deorphanizing Strategiesmentioning

confidence: 99%

More than two decades of research on insect neuropeptide GPCRs: an overview

Caers¹,

Verlinden²,

Zels³

et al. 2012

Front. Endocrin.

151

143

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This review focuses on the state of the art on neuropeptide receptors in insects. Most of these receptors are G protein-coupled receptors (GPCRs) and are involved in the regulation of virtually all physiological processes during an insect's life. More than 20 years ago a milestone in invertebrate endocrinology was achieved with the characterization of the first insect neuropeptide receptor, i.e., the Drosophila tachykinin-like receptor. However, it took until the release of the Drosophila genome in 2000 that research on neuropeptide receptors boosted. In the last decade a plethora of genomic information of other insect species also became available, leading to a better insight in the functions and evolution of the neuropeptide signaling systems and their intracellular pathways. It became clear that some of these systems are conserved among all insect species, indicating that they fulfill crucial roles in their physiological processes. Meanwhile, other signaling systems seem to be lost in several insect orders or species, suggesting that their actions were superfluous in those insects, or that other neuropeptides have taken over their functions. It is striking that the deorphanization of neuropeptide GPCRs gets much attention, but the subsequent unraveling of the intracellular pathways they elicit, or their physiological functions are often hardly examined. Especially in insects besides Drosophila this information is scarce if not absent. And although great progress made in characterizing neuropeptide signaling systems, even in Drosophila several predicted neuropeptide receptors remain orphan, awaiting for their endogenous ligand to be determined. The present review gives a précis of the insect neuropeptide receptor research of the last two decades. But it has to be emphasized that the work done so far is only the tip of the iceberg and our comprehensive understanding of these important signaling systems will still increase substantially in the coming years.

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Select Neuropeptides and their G-Protein Coupled Receptors in Caenorhabditis Elegans and Drosophila Melanogaster

Cited by 17 publications

References 118 publications

The FMRFamide-Like Peptide Family in Nematodes

The FMRFamide-Like Peptide Family in Nematodes

Pharmacological and functional similarities of the human neuropeptide Y system in C. elegans challenges phylogenetic views on the FLP/NPR system

More than two decades of research on insect neuropeptide GPCRs: an overview

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