System-wide mapping of peptide-GPCR interactions in C. elegans

Cell Reports, Journal Year: 2023, Volume and Issue: 42(9), P. 113058 - 113058

Published: Aug. 31, 2023

Neuropeptides and peptide hormones are ancient, widespread signaling molecules that underpin almost all brain functions. They constitute a broad ligand-receptor network, mainly by binding to G protein-coupled receptors (GPCRs). However, the organization of peptidergic network roles many peptides remain elusive, as our insight into peptide-receptor interactions is limited GPCRs still orphan receptors. Here we report genome-wide peptide-GPCR interaction map in Caenorhabditis elegans. By reverse pharmacology screening over 55,384 possible interactions, identify 461 cognate couples uncover with specific complex combinatorial encoded across within single genes. These provide insights functions evolution. Combining dataset phylogenetic analysis supports co-evolution conservation at least 14 bilaterian systems C. This resource lays foundation for system-wide network.

Language: Английский

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Cholecystokinin/sulfakinin peptide signaling: conserved roles at the intersection between feeding, mating and aggression

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(3)

Published: March 1, 2022

Neuropeptides are the most diverse messenger molecules in metazoans and involved regulation of daily physiology a wide array behaviors. Some neuropeptides their cognate receptors structurally functionally well conserved over evolution bilaterian animals. Among these peptides related to gastrin cholecystokinin (CCK). In mammals, CCK is produced by intestinal endocrine cells brain neurons, regulates gall bladder contractions, pancreatic enzyme secretion, gut functions, satiety food intake. Additionally, plays important roles neuromodulation several circuits that regulate reward, anxiety, aggression sexual behavior. invertebrates, CCK-type (sulfakinins, SKs) are, with few exceptions, neurons only. Common among invertebrates SKs mediate ingestion variety mechanisms. Also secretion digestive enzymes has been reported. Studies genetically tractable fly Drosophila have advanced our understanding SK signaling mechanisms feeding, but also gustatory sensitivity, locomotor activity, reproductive A set eight SK-expressing competing males, they integrate internal state external stimuli diminish sex drive increase aggression. The same sugar gustation, induce reduce feeding. Although functional CCK/SK appear between available data suggest underlying differ.

Language: Английский

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A descending inhibitory mechanism of nociception mediated by an evolutionarily conserved neuropeptide system in Drosophila

eLife, Journal Year: 2023, Volume and Issue: 12

Published: March 31, 2023

Nociception is a neural process that animals have developed to avoid potentially tissue-damaging stimuli. While nociception triggered in the peripheral nervous system, its modulation by central system critical mammals, whose dysfunction has been extensively implicated chronic pain pathogenesis. The mechanisms of are largely conserved across animal kingdom. However, it unclear whether brain-mediated also non-mammalian species. Here, we show Drosophila descending inhibitory mechanism from brain, mediated neuropeptide Drosulfakinin (DSK), homolog cholecystokinin (CCK) plays an important role control mammals. We found mutants lacking dsk or receptors hypersensitive noxious heat. Through combination genetic, behavioral, histological, and Ca2+ imaging analyses, subsequently revealed neurons involved DSK-mediated nociceptive regulation at single-cell resolution identified DSKergic neuronal pathway inhibits nociception. This study provides first evidence for modulatory brain species evolutionarily CCK raising possibility inhibition ancient regulate

Language: Английский

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Evolutionary conserved peptide and glycoprotein hormone-like neuroendocrine systems in C. elegans

Molecular and Cellular Endocrinology, Journal Year: 2024, Volume and Issue: 584, P. 112162 - 112162

Published: Jan. 28, 2024

Peptides and protein hormones form the largest group of secreted signals that mediate intercellular communication are central regulators physiology behavior in all animals. Phylogenetic analyses biochemical identifications peptide-receptor systems reveal a broad evolutionary conservation these signaling at molecular level. Substantial progress has been made recent years on characterizing physiological putative ancestral roles many peptide through comparative studies invertebrate models. Several peptides not only molecularly conserved but also have across animal phyla. Here, we focus functional insights gained nematode Caenorhabditis elegans that, with its compact well-described nervous system, provides powerful model to dissect neuroendocrine networks involved control behavior. We summarize discoveries knowledge functions hormone C. elegans.

Language: Английский

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System-wide mapping of neuropeptide-GPCR interactions inC. elegans

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 1, 2022

Summary Neuropeptides are ancient, widespread signaling molecules that underpin almost all brain functions. They constitute a broad ligand-receptor network, mainly by binding to G protein-coupled receptors (GPCRs). However, the organization of peptidergic network and roles many neuropeptides remain elusive, as our insight into neuropeptide-receptor interactions is limited peptide GPCRs in animal models humans still orphan receptors. Here we report genome-wide neuropeptide-GPCR interaction map C. elegans . By reverse pharmacology screening over 55,384 possible interactions, identify 461 cognate peptide-GPCR couples uncover with specific complex combinatorial encoded across within single genes. These provide insights neuropeptide functions evolution. Combining dataset phylogenetic analysis supports peptide-receptor co-evolution conservation at least 14 bilaterian systems This resource lays foundation for system-wide network. Highlights System-wide deorphanizes 68 Discovery pairs additional ligands characterized show receptor Peptide-GPCR support long-range expansion

Language: Английский

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Morphological and Physiological Aspects of Mutable Collagenous Tissue at the Autotomy Plane of the Starfish Asterias rubens L. (Echinodermata, Asteroidea): An Echinoderm Paradigm

Marine Drugs, Journal Year: 2023, Volume and Issue: 21(3), P. 138 - 138

Published: Feb. 22, 2023

The mutable collagenous tissue (MCT) of echinoderms has the capacity to undergo changes in its tensile properties within a timescale seconds under control nervous system. All echinoderm autotomy (defensive self-detachment) mechanisms depend on extreme destabilisation structures at plane separation. This review illustrates role MCT by bringing together previously published and new information basal arm starfish Asterias rubens L. It focuses components breakage zones dorsolateral ambulacral regions body wall, details data their structural organisation physiology. Information is also provided extrinsic stomach retractor apparatus whose involvement not been recognised. We show that A. tractable model system for addressing outstanding problems biology. amenable vitro pharmacological investigations using isolated preparations provides an opportunity application comparative proteomic analysis other “-omics” methods which are aimed molecular profiling different mechanical states characterising effector cell functions.

Language: Английский

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Localization of Cholecystokinin/Sulfakinin Neuropeptides in Biomphalaria glabrata, an Intermediate Host for Schistosomiasis

The Journal of Comparative Neurology, Journal Year: 2025, Volume and Issue: 533(1)

Published: Jan. 1, 2025

Snails belonging to the genus Biomphalaria serve as obligatory intermediate hosts for trematode Schistosoma mansoni, causative agent most widespread form of schistosomiasis. The simpler nervous systems gastropod molluscs, such Biomphalaria, provide advantageous models investigating neural responses infection at cellular and network levels. present study examined neuropeptides related cholecystokinin (CCK), a major multifunctional regulator central system (CNS) function in mammals. A transcriptome generated from CNS alexandrina included transcript encoding two CCK-related peptides, designated Balex-CCK1 (pEGEWSYDY(SO 3 H)GLGGGRF-NH2) Balex-CCK2 (NYGDY(SO H)GIGGGRF-NH2). Peptide expression was glabrata mRNA level using hybridization chain reaction (HCR) protocol protein an antibody against Balex-CCK1. Expression detected 60-70 neurons distributed throughout CNS, well profuse fiber connecting ganglia projecting periphery. CCK-like immunoreactive (CCKli) fibers were also observed on organs associated with cardiorespiratory (nephridium, mantle, gill) male reproductive systems. comparison peptide localization suggested that CCK could be regulated translation. potential role these peptides mediating by larval schistosomes is discussed.

Language: Английский

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The Neuropeptide Sulfakinin, a peripheral regulator of insect behavioral switch between mating and foraging

Published: Feb. 14, 2025

Behavioral strategies for foraging and reproduction in the oriental fruit fly ( Bactrocera dorsalis ) are alternative options resource allocation controlled by neuropeptides. Here we show that behavioral switch between is associated with changes antennal sensitivity. Starved flies became more sensitive to food odors while suppressing their response opposite-sex pheromones. The gene encoding sulfakinin receptor 1 SkR1 was significantly upregulated antennae of starved flies, so tested phenotypes null mutants genes skr1 −/− its ligand sk ). In both knockout lines, responses shifted mating mode even when were starved. This suggests signaling via promotes mating. Further analysis mutant revealed sets odorant (OR) differentially expressed. Functional characterization expressed ORs suggested directly suppresses expression respond hormones enhancing detect volatiles. We conclude SkR1, modulating OR expressions leading altered antenna sensitivities, an important component starvation-dependent change.

Language: Английский

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The neuropeptidomes of the sea cucumbers Stichopus cf. horrens and Holothuria scabra

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 27, 2025

The Philippines is a renowned marine biodiversity hotspot, home to several sea cucumber species with unusual biological traits. Among these, Stichopus cf. horrens notable for its ability undergo rapid body wall liquefaction when stressed, coupled remarkable regenerative abilities. In contrast, Holothuria scabra has one of the most robust walls in cucumbers and thrives many regimes tropics. Despite their intriguing traits, neurobiology chemical diversity these remain underexplored. Neuropeptides are important components an animal's neurobiological toolkit that underlie various physiological behavioral processes. Thus, discovery neuropeptides crucial step understanding molecular underpinnings unique traits cucumbers. Leveraging throughput sensitivity tandem mass spectrometry, we obtained unbiased view endogenous peptidomes radial nerve cord tissues non-model species, H. S. horrens. this work, sequenced 60 mature peptides from were derived 22 precursor proteins, 43 originating 25 proteins nervous tissues. A total seven previously unannotated uncharacterized neuropeptide precursors identified, thereby expanding known animal repertoire. Furthermore, discovered consistent structural features based on type post-translational modifications while pushing forward potentially novel proteolytic processing sites during peptide maturation enriched flanking amino acid residues. Collectively, our results provide preliminary data expand echinoderm through discovery, paving way innovative solutions address global demand echinoderms.

Language: Английский

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Identification and characterization of neuropeptides in sea urchin Strongylocentrotus intermedius

General and Comparative Endocrinology, Journal Year: 2025, Volume and Issue: unknown, P. 114716 - 114716

Published: March 1, 2025

Language: Английский

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