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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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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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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Discovery and functional characterization of a bombesin-type neuropeptide signaling system in an invertebrate

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(13)

Published: March 28, 2025

Neuropeptide signaling systems are key regulators of physiological and behavioral processes in animals. However, the evolutionary history some neuropeptides originally discovered vertebrates is unknown. The peptide bombesin (BN) was first isolated from skin toad Bombina bombina subsequently BN-related have been identified other chordates, including gastrin-releasing (GRP) neuromedin B (NMB) mammals, a GRP-like cephalochordate Branchiostoma japonicum . BN-type hitherto not any nonchordate Here, we report discovery functional characterization neuropeptide system an echinoderm—the starfish Asterias rubens precursor proteins were several echinoderm species based on their amino acid sequences gene structures, mature structure A. ArBN determined using mass spectrometry. A protein related to vertebrate GRP/NMB-type G protein–coupled receptors experimentally as receptor for Analysis distribution mRNA situ hybridization immunohistochemistry revealed widespread pattern expression central nervous system, digestive locomotory organs. Moreover, effects included contraction retraction evertible stomach inhibition feeding behavior. Our findings show that can be traced back deuterostome common ancestor echinoderms chordates. Furthermore, ancient role behavior has revealed.

Language: Английский

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Decoding Neuropeptide Complexity: Advancing Neurobiological Insights from Invertebrates to Vertebrates through Evolutionary Perspectives

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Neuropeptides are vital signaling molecules involved in neural communication, hormonal regulation, and stress response across diverse taxa. Despite their critical roles, neuropeptide research remains challenging due to low abundance, complex post-translational modifications (PTMs), dynamic expression patterns. Mass spectrometry (MS)-based neuropeptidomics has revolutionized peptide identification quantification, enabling the high-throughput characterization of neuropeptides PTMs. However, complexity vertebrate networks poses significant challenges for functional studies. Invertebrate models, such as Cancer borealis, Drosophila melanogaster, Caenorhabditis elegans, offer simplified circuits, well-characterized systems, experimental tools elucidating roles neuropeptides. These models have revealed conserved families, including allatostatins, RFamides, tachykinin-related peptides, whose homologues regulate analogous physiological functions. Recent advancements MS techniques, ion mobility MALDI imaging, further enhanced spatial temporal resolution analysis, allowing insights into systems. not only expands our understanding functions but also informs translational applications development peptide-based therapeutics. This review highlights utility invertebrate discovery, emphasizing contributions uncovering fundamental biological principles relevance

Language: Английский

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Reconstructing the Origins of the Somatostatin and Allatostatin-C Signaling Systems Using the Accelerated Evolution of Biodiverse Cone Snail Toxins

Molecular Biology and Evolution, Journal Year: 2022, Volume and Issue: 39(4)

Published: April 1, 2022

Abstract Somatostatin and its related peptides (SSRPs) form an important family of hormones with diverse physiological roles. The ubiquitous presence SSRPs in vertebrates several invertebrate deuterostomes suggests ancient origin the SSRP signaling system. However, existence genes outside has not been established, evolutionary history this system remains poorly understood. Our recent discovery SSRP-like toxins (consomatins) venomous marine cone snails (Conus) suggested a mollusks potentially other protostomes. Here, we identify molluscan gene that gave rise to consomatin family. Following recruitment into venom, experienced strong positive selection repeated duplications resulting formation hyperdiverse venom peptides. Intriguingly, largest number consomatins was found worm-hunting species (>400 sequences), indicating homologous annelids, another large protostome phylum. Consistent this, comprehensive sequence mining enabled identification sequences (and their corresponding orphan receptor) annelids phyla. These results established many major branches bilaterians challenge prevailing hypothesis deuterostome allatostatin-C are orthologous peptide families. Finally, having set predator–prey available, show although snail’s under purifying selection, experience rapid directional target receptors changing mix prey.

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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Evolution of Hypothalamic–Pituitary Neuropeptides and Their Receptors: Insights from Invertebrates

Masterclass in neuroendocrinology, Journal Year: 2025, Volume and Issue: unknown, P. 45 - 70

Published: Jan. 1, 2025

Language: Английский

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Localization of relaxin‐like gonad‐stimulating peptide expression in starfish reveals the gonoducts as a source for its role as a regulator of spawning

The Journal of Comparative Neurology, Journal Year: 2023, Volume and Issue: 531(13), P. 1299 - 1316

Published: May 22, 2023

Abstract Oocyte maturation and gamete release (spawning) in starfish are triggered by relaxin‐like gonad‐stimulating peptide (RGP), a neuropeptide that was first isolated from the radial nerve cords of these animals. Hitherto, it has generally been assumed source RGP triggers spawning physiologically. To investigate other sources RGP, here we report comprehensive anatomical analysis its expression, using both situ hybridization immunohistochemistry to map precursor transcripts respectively, Asterias rubens . Cells expressing were revealed ectoneural epithelium circumoral ring, arm tips, tube feet, cardiac stomach, pyloric and, most notably, gonoducts. Using specific antibodies A. immunostaining cells and/or fibers region terminal tentacle tip‐associated structures, body wall, peristomial membrane, esophagus, caeca, Our discovery is expressed gonoducts proximal gonadotropic site action gonads important because provides new perspective on how may act as gonadotropin starfish. Thus, hypothesize starfish, while produced parts regulate physiological/behavioral processes.

Language: Английский

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Receptor deorphanization in an echinoderm reveals kisspeptin evolution and relationship with SALMFamide neuropeptides

BMC Biology, Journal Year: 2022, Volume and Issue: 20(1)

Published: Aug. 24, 2022

Abstract Background Kisspeptins are neuropeptides that regulate reproductive maturation in mammals via G-protein-coupled receptor-mediated stimulation of gonadotropin-releasing hormone secretion from the hypothalamus. Phylogenetic analysis kisspeptin-type receptors indicates this neuropeptide signaling system originated a common ancestor Bilateria, but little is known about kisspeptin invertebrates. Results Contrasting with occurrence single receptor mammalian species, here, we report discovery an expanded family eleven deuterostome invertebrate — starfish Asterias rubens (phylum Echinodermata). Furthermore, derived four precursor proteins were identified as ligands for six these receptors. One or more kisspeptin-like two (ArKPP1, ArKPP2) act A. (ArKPR1,3,8,9). muscle relaxants echinoderms (SALMFamides) (ArKPR6,7). The SALMFamide S1 (or ArS1.4) and ‘cocktail’ seven protein (ArS1.1-ArS1.7) ArKPR7. S2 ArS2.3) eight (ArS2.1-ArS2.8) ArKPR6. Conclusions Our findings reveal remarkable diversity provide important new insights into evolution signaling. hitherto unknown relationship kisspeptins SALMFamides, discovered prior to identification mammals, presents radical change perspective research on

Language: Английский

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