NPF activates a specific NPF receptor and regulates food intake in Pacific abalone Haliotis discus hannai DOI Creative Commons

Kyeong Seop Kim,

Mi Ae Kim, Keunwan Park

et al.

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: Oct. 22, 2021

Abstract Neuropeptides function through G protein-coupled receptors (GPCRs) with high specificity, implying a significant degree of neuropeptide-GPCR coevolution. However, potential neuropeptide signaling systems in non-chordates are relatively elusive. We determined the specificity F (Hdh-NPF) system cognate receptor (Hdh-NPFR) Pacific abalone, Haliotis discus hannai . Phylogenetic and exon–intron arrangement analyses bilaterian NPF chordate ortholog NPY their sequences revealed likely common ancestor, Hdh-NPFR was similar to NPYR2 subtype among NPYR1, NPYR2, NPYR5 subtypes. Among four Hdh-NPFR-related receptors, specifically responded Hdh-NPF peptide, supported by dose–response luciferase reporter curve, intracellular Ca 2+ mobilization, phosphorylation ERK1/2 its inhibition protein kinase C inhibitor. Peptide fragmentations shuffling human could not activate cellular response Hdh-NPFR. Three-dimensional silico modeling suggested that interaction C-terminal amino acids extracellular loops is critical for activation. In vivo injection peptide increased food consumption, knockdown expression decreased consumption abalone. These findings provide evidence co-evolution NPF/Y ligand-receptor system, enabling further research on mollusk orexigenic neuropeptides.

Language: Английский

The neuropeptide FLP-11 induces and self-inhibits sleep through the receptor DMSR-1 in Caenorhabiditis elegans DOI Creative Commons
Lorenzo Rossi,

Kingsley Kwaku Amoako,

Inka Busack

et al.

Current Biology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Reconstructing the Origins of the Somatostatin and Allatostatin-C Signaling Systems Using the Accelerated Evolution of Biodiverse Cone Snail Toxins DOI Creative Commons
Thomas Lund Koch, Iris Bea L. Ramiro, Paula Flórez Salcedo

et al.

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

Citations

17
Large-scale deorphanization of Nematostella vectensis neuropeptide G protein-coupled receptors supports the independent expansion of bilaterian and cnidarian peptidergic systems DOI Creative Commons
Daniel Thiel, Luis Alfonso Yañez Guerra, Amanda Kieswetter

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: May 10, 2024

Neuropeptides are ancient signaling molecules in animals but only few peptide receptors known outside bilaterians. Cnidarians possess a large number of G protein-coupled (GPCRs) – the most common bilaterian neuropeptides these remain orphan with no ligands. We searched for sea anemone Nematostella vectensis and created library 64 peptides derived from 33 precursors. In large-scale pharmacological screen 161 N. GPCRs, we identified 31 specifically activated by 1 to 3 14 peptides. Mapping GPCR neuropeptide expression single-cell sequencing data revealed how cnidarian tissues extensively connected multilayer peptidergic networks. Phylogenetic analysis direct orthology systems supports independent expansion cnidarians ancestral peptide-receptor pairs.

Language: Английский

Citations

3
GPR139, an Ancient Receptor and an Emerging Target for Neuropsychiatric and Behavioral Disorders DOI Creative Commons
Minyu Chan, Satoshi Ogawa

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Abstract GPR139 is an orphan G-protein-coupled receptor that predominantly expressed in several midbrain regions, e.g., the habenula, striatum, and hypothalamus. gene highly conserved across vertebrate phylogenetic taxa, suggesting its fundamental importance neurophysiology. Evidence from both animal studies human genetic association has demonstrated dysregulation of expression function linked to aberrant behaviors, cognitive deficits, alterations sleep alertness, substance abuse withdrawal. Animal knockout models suggest plays anti-opioid role by modulating signaling activity μ-opioid (MOR), as well intensity withdrawal symptoms nociception behavioral paradigms. Modulation surrogate agonists such TAK-041 JNJ-63533054 shown promising results experimental models; however, use clinical trials produced heterogeneous effects not met intended primary endpoint. Here, we highlight current vitro vivo GPR139, potential physiological roles, therapeutic pathophysiology neuropsychiatric disorders. This review aims focus on knowledge gaps facilitate future will contribute understanding a target for

Language: Английский

Citations

0
Two distinct compartments of a ctenophore comb plate provide structural and functional integrity for the motility of giant multicilia DOI Creative Commons
Kei Jokura,

Yu Sato,

Kogiku Shiba

et al.

Current Biology, Journal Year: 2022, Volume and Issue: 32(23), P. 5144 - 5152.e6

Published: Oct. 21, 2022

Language: Английский

Citations

13
Discovery and functional characterization of neuropeptides in crinoid echinoderms DOI Creative Commons
Alessandra Aleotti, Iain C. Wilkie, Luis Alfonso Yañez Guerra

et al.

Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Dec. 13, 2022

Neuropeptides are one of the largest and most diverse families signaling molecules in animals and, accordingly, they regulate many physiological processes behaviors. Genome transcriptome sequencing has enabled identification genes encoding neuropeptide precursor proteins species from a growing variety taxa, including bilaterian non-bilaterian animals. Of particular interest deuterostome invertebrates such as phylum Echinodermata, which occupies phylogenetic position that facilitated reconstruction evolution systems Bilateria. However, our knowledge echinoderms is largely based on bioinformatic experimental analysis eleutherozoans-Asterozoa (starfish brittle stars) Echinozoa (sea urchins sea cucumbers). Little known about crinoids (feather stars lilies), sister clade to Eleutherozoa. Therefore, we have analyzed transcriptome/genome sequence data three feather star species, Anneissia japonica, Antedon mediterranea, Florometra serratissima, produce first comprehensive precursors crinoids. These include representatives several predicted crinoid precursors. Using A. mediterranea an model, investigated expression selected neuropeptides larvae (doliolaria), post-metamorphic pentacrinoids adults, providing new insights into cellular architecture nervous systems. Thus, using mRNA situ hybridization F-type SALMFamide transcripts were revealed previously undescribed population peptidergic cells located dorso-laterally doliolaria. Furthermore, immunohistochemistry calcitonin-type was aboral nerve center, circumoral ring oral tube feet ectoneural entoneural compartments system adults. Moreover, functional vasopressin/oxytocin-type (crinotocin), expressed brachial arms this peptide causes dose-dependent change mechanical behavior arm preparations vitro-the reported biological action crinoid. In conclusion, findings provide perspectives foundations for further exploration expression/function eleutherozoan echinoderms.

Language: Английский

Citations

13
Neuropeptides and degenerin/epithelial Na + channels: a relationship from mammals to cnidarians DOI Creative Commons
Stefan Gründer,

Audrey Ortega Ramírez,

Gáspár Jékely

et al.

The Journal of Physiology, Journal Year: 2022, Volume and Issue: 601(9), P. 1583 - 1595

Published: Nov. 22, 2022

Ion channels of the degenerin (DEG)/epithelial Na+ channel (ENaC) family serve diverse functions ranging from mechanosensation over reabsorption to H+ sensing and neurotransmission. However, several DEG/ENaCs interact with neuropeptides; some are directly activated, whereas others modulated by neuropeptides. Two questions arise: does this interaction have a common structural basis it an ancient origin? Current evidence suggests that RFamide neuropeptides activate FMRFamide-activated (FaNaCs) invertebrates via binding pocket at external face their large extracellular domain. It is likely RFamides might freshwater polyp Hydra (the HyNaCs) similar pocket, although there not yet any experimental evidence. In contrast, modulate acid-sensing ion (ASICs) vertebrates central cavity enclosed β-sheets Dynorphin opioid peptides, for part, bind acidic ASICs, which be evolutionarily related peptide FaNaCs, but instead opening they work as antagonists stabilize its closed state. Moreover, peptides interacting animals different phyla, having sequences, unrelated each other. Collectively, appears despite seemingly has bases many origins.

Language: Английский

Citations

12
Egg-laying hormone expression in identified neurons across developmental stages and reproductive states of the nudibranch Berghia stephanieae DOI Creative Commons
Cheyenne Tait, M. Desmond Ramirez, Paul S. Katz

et al.

Hormones and Behavior, Journal Year: 2024, Volume and Issue: 164, P. 105578 - 105578

Published: June 25, 2024

Neuropeptides play essential roles in coordinating reproduction. Egg-laying hormone (ELH) is conserved genetic sequence and behavioral function across molluscs, where neuronal clusters secrete ELH to modulate induce egg-laying. Here we investigated the nudibranch mollusc, Berghia stephanieae. preprohormone gene orthologs, which showed clade-specific differences at C-terminus of predicted bioactive peptide, were identified brain transcriptomes several nudipleuran species, including B. shares deep homology with corticotropin-releasing family, has broadly stress response. Injection synthesized stephanieae peptide into mature individuals induced expression body was mapped using in-situ hybridization chain reaction. Across adult brain, 300-400 neurons expressed ELH. Twenty-one different cell types adults, three located unilaterally on right side, corresponds location reproductive organs. Ten present pre-reproductive juvenile stages. An asymmetric cluster approximately 100 small appeared pedal ganglion late-stage juveniles. Additional pleural ganglia only adults that actively laying eggs sub-adults verge doing so, implicating their direct role Outside sensory appendages, presumptive neurons. Its widespread suggests plays a beyond reproduction gastropod molluscs.

Language: Английский

Citations

2
Functional Characterization of Gonadotropin-Releasing Hormone and Corazonin Signaling Systems in Pacific Abalone: Toward Reclassification of Invertebrate Neuropeptides DOI
Mi Ae Kim,

Tae Ha Kim,

Priyadharshini Kannan

et al.

Neuroendocrinology, Journal Year: 2023, Volume and Issue: 114(1), P. 64 - 89

Published: Sept. 13, 2023

<b><i>Introduction:</i></b> The proposed evolutionary origins and corresponding nomenclature of bilaterian gonadotropin-releasing hormone (GnRH)-related neuropeptides have changed tremendously with the aid receptor deorphanization. However, reclassification GnRH corazonin (CRZ) signaling systems in Lophotrochozoa remains unclear. <b><i>Methods:</i></b> We characterized CRZ receptors mollusk Pacific abalone, <i>Haliotis discus hannai</i> (Hdh), by phylogenetic gene expression analyses, bioluminescence-based reporter, Western blotting, substitution peptide amino acids, vivo neuropeptide injection, RNA interference assays. <b><i>Results:</i></b> Two Hdh CRZ-like (Hdh-CRZR-A Hdh-CRZR-B) three GnRH-like (Hdh-GnRHR1-A, Hdh-GnRHR1-B, Hdh-GnRHR2) were identified. In analysis, Hdh-CRZR-A -B grouped within CRZ-type receptors, whereas Hdh-GnRHR1-A/-B Hdh-GnRHR2 clustered GnRH/adipokinetic (AKH)/CRZ-related peptide-type receptors. Hdh-CRZR-A/-B Hdh-GnRHR1-A activated Hdh-CRZ (pQNYHFSNGWHA-NH<sub>2</sub>) Hdh-GnRH (pQISFSPNWGT-NH<sub>2</sub>), respectively. dually coupled Gα<sub>q</sub> Gα<sub>s</sub> pathways, was linked only signaling. Analysis substituted peptides, [I<sup>2</sup>S<sup>3</sup>]Hdh-CRZ [N<sup>2</sup>Y<sup>3</sup>H<sup>4</sup>]Hdh-GnRH, silico docking models revealed that N-terminal acids peptides are critical for selectivity Hdh-CRZR Hdh-GnRHR. precursor transcripts their mainly expressed neural ganglia, levels increased starved abalones. Injection into abalones decreased food consumption, knockdown consumption. Moreover, induced germinal vesicle breakdown mature oocytes. <b><i>Conclusion:</i></b> Characterization Hdh-CRZRs Hdh-GnRHRs cognate provides new insight route GnRH-related bilaterians.

Language: Английский

Citations

6
Functional analysis of LFRFamide signaling in Pacific abalone, Haliotis discus hannai DOI Creative Commons

Sungwoo Yoon,

Mi Ae Kim, Jung Sick Lee

et al.

PLoS ONE, Journal Year: 2022, Volume and Issue: 17(5), P. e0267039 - e0267039

Published: May 5, 2022

The invertebrate LFRFamide (LFRFa) and short neuropeptide F (sNPF), consisting of 6 to 10 amino acids, are orthologs for bilaterian NPF/Y, which consist 36 40 acids. Recently, a molluscan G protein-coupled receptor (GPCR) NPF was characterized in Pacific abalone ( Haliotis discus hannai ). To address the functional evolutionary route LFRFa signaling system, this study, we identified cDNAs encoding precursors sNPF (Hdh-sNPFR) abalone. Four mature peptides with or 7 acids were predicted: GSLFRFa, GGLFRFa, GTLFRFa, GSTLFRFa. Hdh-sNPFR as classical rhodopsin-like GPCR classified into sNPFR group. In HEK293 cells, mainly localized cell membranes internalized cytoplasm following treatment peptides. Reporter assays demonstrated that inhibit forskolin-stimulated cAMP accumulation Hdh-sNPFR-expressing cells. precursor transcripts more strongly expressed cerebral pleural-pedal ganglia than peripheral tissues such ovary, gills, intestine, hepatopancreas. levels hepatopancreas significantly higher female immature females. Injection induced egg release spawning behavior abalone, but suppressed food intake. These results suggest endogenous ligands involved intake reproduction through Gαi-protein dependent pathway.

Language: Английский

Citations

9