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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Machine learning and AI-based approaches for bioactive ligand discovery and GPCR-ligand recognition

Methods, Journal Year: 2020, Volume and Issue: 180, P. 89 - 110

Published: July 6, 2020

In the last decade, machine learning and artificial intelligence applications have received a significant boost in performance attention both academic research industry. The success behind most of recent state-of-the-art methods can be attributed to latest developments deep learning. When applied various scientific domains that are concerned with processing non-tabular data, for example, image or text, has been shown outperform not only conventional but also highly specialized tools developed by domain experts. This review aims summarize AI-based GPCR bioactive ligand discovery particular focus on achievements trends. To make this article accessible broad audience computational scientists, we provide instructive explanations underlying methodology, including overviews commonly used architectures feature representations molecular data. We highlight led successful ligands. However, an equal is discussion learning-based technology general potential pave way future. concludes brief outlook highlighting trends learning, such as active semi-supervised which great advancing discovery.

Language: Английский

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Mass spectrometry of short peptides reveals common features of metazoan peptidergic neurons

Nature Ecology & Evolution, Journal Year: 2022, Volume and Issue: 6(10), P. 1438 - 1448

Published: Aug. 8, 2022

Abstract The evolutionary origins of neurons remain unknown. Although recent genome data extant early-branching animals have shown that neural genes existed in the common ancestor animals, physiological and genetic properties early phase are still unclear. Here, we performed a mass spectrometry-based comprehensive survey short peptides from lineages Cnidaria, Porifera Ctenophora. We identified number mature ctenophore neuropeptides expressed associated with sensory, muscular digestive systems. stored vesicles cell bodies neurites, suggesting volume transmission similar to cnidarian bilaterian peptidergic A comparison characteristics revealed peptide-expressing cells Cnidaria Ctenophora express vast majority pivotal roles maturation, secretion degradation Bilateria. Functional analysis prediction receptors machine learning demonstrated peptide regulation wide range target effector cells, including striking parallels between neuronal Bilateria those Ctenophora, most basal neuron-bearing suggest origin metazoan nervous

Language: Английский

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The regulation of oocyte maturation and ovulation in the closest sister group of vertebrates

eLife, Journal Year: 2019, Volume and Issue: 8

Published: Oct. 1, 2019

Ascidians are the closest living relatives of vertebrates, and their study is important for understanding evolutionary processes oocyte maturation ovulation. In this study, we first examined ovulation Ciona intestinalis Type A by monitoring follicle rupture in vitro, identifying a novel mechanism neuropeptidergic regulation vasopressin family peptide (CiVP) directly upregulated phosphorylation extracellular signal–regulated kinase (CiErk1/2) via its receptor. CiVP ultimately activated maturation-promoting factor, leading to germinal vesicle breakdown. CiErk1/2 also induced expression matrix metalloproteinase (CiMMP2/9/13) oocyte, resulting collagen degradation outer follicular cell layer liberation fertile oocytes from ovary. This demonstration essential pathways regulating ascidians will facilitate investigations process peptidergic throughout phylum Chordata.

Language: Английский

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Invertebrate Gonadotropin-Releasing Hormone Receptor Signaling and Its Relevant Biological Actions

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(22), P. 8544 - 8544

Published: Nov. 12, 2020

Gonadotropin-releasing hormones (GnRHs) play pivotal roles in reproduction via the hypothalamus-pituitary-gonad axis (HPG axis) vertebrates. GnRHs and their receptors (GnRHRs) are also conserved invertebrates lacking HPG axis, indicating that invertebrate do not serve as "gonadotropin-releasing factors" but, rather, function neuropeptides directly regulate target tissues. All vertebrate urochordate comprise 10 amino acids, whereas amphioxus, echinoderm, protostome GnRH-like peptides 11- or 12-residue peptides. Intracellular calcium mobilization is major second messenger for GnRH signaling cephalochordates, echinoderms, protostomes, while GnRHRs stimulate cAMP production pathways. Moreover, ligand-specific modulation of signal transduction heterodimerization between GnRHR paralogs indicates species-specific evolution Ciona intestinalis. The characterization authentic putative various tissues vitro vivo activities indicate responsible regulation both reproductive nonreproductive functions. In this review, we examine our current understanding perspectives on primary sequences, tissue distribution mRNA expression, transduction, biological functions receptors.

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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Draft genome of Tanacetum cinerariifolium, the natural source of mosquito coil

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: Dec. 3, 2019

Abstract Pyrethrum ( Tanacetum cinerariifolium ), which is a perennial Asteraceae plant with white daisy-like flowers, the original source of mosquito coils and known for biosynthesis pyrethrin class natural insecticides. However, molecular basis production pyrethrins by T. has yet to be fully elucidated. Here, we present 7.1-Gb draft genome , consisting 2,016,451 scaffolds 60,080 genes predicted high confidence. Notably, analyses transposable elements (TEs) indicated that TEs occupy 33.84% sequence. Furthermore, sire oryco clades were found enriched in -specific evolutionary lineage, occupying total 13% sequence, proportion approximately 8-fold higher than other plants. InterProScan analysis demonstrated biodefense-related toxic proteins (e.g., ribosome inactivating proteins), signal transduction-related histidine kinases), metabolic enzymes lipoxygenases, acyl-CoA dehydrogenases/oxygenases, P450s) are also highly genome. Molecular phylogenetic detected variety genus-specific multiplication, including both common others appear specific biosynthesis. Together, these data identify possible novel components pathway provide new insights into unique genomic features .

Language: Английский

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The ventral peptidergic system of the adult ascidian Ciona robusta (Ciona intestinalis Type A) insights from a transgenic animal model

Scientific Reports, Journal Year: 2020, Volume and Issue: 10(1)

Published: Feb. 5, 2020

Abstract Ascidians are the sister group of vertebrates and occupy a critical position in explorations evolution endocrine nervous systems chordates. Here, we describe complete ventral peptidergic system adult transgenic Ciona robusta ( intestinalis Type A) which expresses Kaede reporter gene driven by prohormone convertase 2 (PC2) promoter. Numerous PC2 promoter-driven fluorescent (Kaede-positive) non-neural cells were distributed blood sinus located at anterior end pharynx, suggesting acquisition circulatory . Kaede-positive ciliated columnar cells, rounded tall observed alimentary organs, including endostyle, esophagus, stomach, intestine, that digestive functions regulated multiple systems. In heart, neurons ring-shaped plexus both ends myocardium. Nerve fiber–like tracts ran along raphe appeared to be connected with plexuses. Such unique structures suggest role for cardiac function. Collectively, present anatomic analysis revealed major framework , could facilitate investigations regulation tissues, heart.

Language: Английский

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Comparative Aspects of Structure and Function of Cnidarian Neuropeptides

Frontiers in Endocrinology, Journal Year: 2020, Volume and Issue: 11

Published: May 27, 2020

Cnidarians are early-branching animals in the eukaryotic tree of life. The phylum Cnidaria divided into five classes: Scyphozoa (true jellyfish), Cubozoa (box Hydrozoa (species, Hydra and Hydractinia), Anthozoa (sea anemone, corals, sea pen), Staurozoa (stalked jellyfish). Peptides play important roles as signaling molecules development differentiation cnidaria. For example, cnidaria use peptides for cell-to cell communication. Recent discoveries show that neuropeptides control several biological processes including muscle contraction, neuron differentiation, metamorphosis. Here, I describe structure functions other cnidarian species. also discuss so-called primitive nervous system is more complex than generally believed.

Language: Английский

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Identifying Receptors for Neuropeptides and Peptide Hormones: Challenges and Recent Progress

ACS Chemical Biology, Journal Year: 2021, Volume and Issue: 16(2), P. 251 - 263

Published: Feb. 4, 2021

Intercellular signaling events mediated by neuropeptides and peptide hormones represent important targets for both basic science drug discovery. For many bioactive peptides, the protein receptors that transmit information across receiving cell membrane are not known, severely limiting these pathways as potential therapeutic targets. Identifying receptor(s) a given of interest is complicated several factors. Most notably, cell–cell peptides generated through dynamic biosynthetic pathways, can act on different families receptor proteins, participate in complex ligand–receptor interactions extend beyond simple one-to-one archetype. Here, we discuss recent methodological advances to identify partners peptides. Recent efforts have centered methods candidate via transcript expression, match peptide–receptor pairs high throughput screening, capture direct using chemical probes. Future applications identification approaches discussed here, well technical advancements address their limitations, promise lead greater understanding how cells communicate deliver physiologies. Importantly, such will likely provide novel treatment human diseases within central nervous endocrine systems.

Language: Английский

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