Functional analysis in a model sea anemone reveals phylogenetic complexity and a role in cnidocyte discharge of DEG/ENaC ion channels

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Jan. 6, 2023

Ion channels of the DEG/ENaC family share a similar structure but serve strikingly diverse biological functions, such as Na

Language: Английский

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Structure and mechanism of a neuropeptide-activated channel in the ENaC/DEG superfamily

Nature Chemical Biology, Journal Year: 2023, Volume and Issue: 19(10), P. 1276 - 1285

Published: Aug. 7, 2023

Language: Английский

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Structural basis for excitatory neuropeptide signaling

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(4), P. 717 - 726

Published: Feb. 9, 2024

Rapid signaling between neurons is mediated by ligand-gated ion channels, cell-surface proteins with an extracellular ligand-binding domain and a membrane-spanning channel domain. The degenerin/epithelial sodium (DEG/ENaC) superfamily diverse in terms of its gating stimuli, some DEG/ENaCs gated neuropeptides, others pH, mechanical force or enzymatic activity. mechanism which ligands bind to activate poorly understood. Here we dissected the structural basis for neuropeptide-gated activity DEG/ENaC, FMRFamide-gated 1 (FaNaC1) from annelid worm Malacoceros fuliginosus, using cryo-electron microscopy. Structures FaNaC1 ligand-free resting state several ligand-bound states reveal site capture ligand-induced conformational changes gating, verified complementary mutagenesis experiments. Our results illuminate offer template experimental dissection pharmacology conduction.

Language: Английский

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Function and phylogeny support the independent evolution of an ASIC-like Deg/ENaC channel in the Placozoa

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Sept. 18, 2023

ASIC channels are bilaterian proton-gated sodium belonging to the large and functionally-diverse Deg/ENaC family that also includes peptide- mechanically-gated channels. Here, we report non-bilaterian invertebrate Trichoplax adhaerens possesses a proton-activated channel, TadNaC2, with unique combination of biophysical features including tachyphylaxis like ASIC1a, reduced proton sensitivity ASIC2a, biphasic macroscopic currents ASIC3, as well low channel blocker amiloride Ca2+ ions. Structural modeling mutation analyses reveal TadNaC2 gating is different from channels, lacking key molecular determinants, involving residues within palm finger regions. Phylogenetic analysis reveals monophyletic clade T. which phylogenetically distinct instead forming BASIC Altogether, this work suggests ASIC-like evolved independently in its phylum Placozoa. Our phylogenetic identifies several clades uncharacterized metazoan provides evidence for existence outside Metazoa, present gene data select unicellular heterokont filasterea-related species.

Language: Английский

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Review: The evolution of peptidergic signaling in Cnidaria and Placozoa, including a comparison with Bilateria

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 23, 2022

Bilateria have bilateral symmetry and are subdivided into Deuterostomia (animals like vertebrates) Protostomia insects mollusks). Neuropeptides occur in both Proto- they frequently structurally related across these two lineages. For example, peptides belonging to the oxytocin/vasopressin family exist clades. The same is true for G protein-coupled receptors (GPCRs) of peptides. These observations suggest that neuropeptides their GPCRs were already present common ancestor Deuterostomia, which lived about 700 million years ago (MYA). Furthermore, early-branching phyla diverged before emergence Bilateria: Cnidaria corals sea anemones), Placozoa (small disk-like animals, feeding on algae). sequences GPCRs, however, not closely those from Bilateria. In addition, cnidarian Placozoa. We propose divergence times between Cnidaria, Placozoa, might be too long recognizing sequence identities. Leucine-rich repeats-containing (LGRs) a special class characterized by N-terminus containing 10-20 leucine-rich domains, used ligand binding. Among ligands LGRs dimeric glycoprotein hormones, insulin-like peptides, such as relaxin. been found only but also early emerging phyla, Humans eight LGRs. our current review, we revisited annotations anemone Nematostella vectensis placozoan Trichoplax adhaerens . identified 13 no less than 46 T All human appear orthologues anemones placozoans. ligands, therefore, evolutionary history, going back

Language: Английский

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Global analysis of ligand-gated ion channel conservation across Platyhelminthes

General and Comparative Endocrinology, Journal Year: 2025, Volume and Issue: unknown, P. 114718 - 114718

Published: March 1, 2025

Ligand-gated ion channels (LGICs) are critical for neurotransmission, mediating responses to neurotransmitters and hormones, influencing diverse physiological processes. This study identifies classifies LGICs across Platyhelminthes, with a particular focus on parasitic neodermatans, which impact human animal health. Using bioinformatics tools, we analyzed from 41 neodermatan species expanded our investigation encompass vertebrates, other invertebrates, non-bilaterians trace LGIC evolutionary pathways Metazoa. We identified 2,269 putative within species, classified into the cys-loop, ASIC/Deg/ENaC, iGluR, P2X families. Our phylogenetic clustering analyses reveal lineage-specific patterns distinct trajectories each family in neodermatans compared free-living platyhelminths taxa. Notably, ASIC/Deg/ENaC displayed greatest degree of neodermatan-specific divergence, while cys-loop families were more conserved To provide insight their potential roles, expression Schistosoma mansoni, revealing widespread neuronal muscle cell types. The distribution acid-sensing (ASICs) both neurons muscles suggests role neuromuscular signalling, receptor (Smp_333600) exhibited sex-specific expression, potentially indicating functional roles males females. Additionally, several acetylcholine GABA receptors showed differential highlighting likely contributions cholinergic inhibitory neurotransmission. These findings underscore relevance parasite physiology, particularly sensory processes, suggest targets antiparasitic interventions.

Language: Английский

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Invertebrate Bile Acid‐Sensitive Ion Channels and Their Emergence in Bilateria

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(8)

Published: April 16, 2025

ABSTRACT The broad Degenerin/epithelial sodium channel (DEG/ENaC) family includes a subfamily of bile acid‐sensing ion channels (BASICs). While their biophysical properties are extensively studied in mammals, the presence and function BASICs invertebrates remain largely unexplored. Here, we present first functional evidence invertebrate BASICs, revealing conserved features evolutionary adaptations across bilaterian species. Using electrophysiological pharmacological approaches, show that exhibit species‐specific acid sensitivity profiles differing responses to blockers, amiloride, diminazene, while retaining shared like inhibition by calcium ions selective permeability ions. For example, acorn worm Schizocardium californicum BASIC displays similar brachiopod Novocrania anomala is activated solely ursodeoxycholic (UDCA) our experiments. Mutagenesis D444 residue pore‐lining region confirms its critical role gating. Combined phylogenetic analysis suggests emerged early evolution, evolving from were merely modulated acids, cousins, into acids. Tissue‐specific expression patterns imply roles acid‐dependent absorption or environmental sensing acid‐like compounds. Given absence endogenous acids invertebrates, propose may detect compounds, contributing ecological interactions. This study enhances understanding evolutionary, functional, with implications for future research native ligands.

Language: Английский

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Large-scale deorphanization of Nematostella vectensis neuropeptide G protein-coupled receptors supports the independent expansion of bilaterian and cnidarian peptidergic systems

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

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Neuropeptides and degenerin/epithelial Na ⁺ channels: a relationship from mammals to cnidarians

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

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A Na+ channel receptor of FMRFamide in the cephalopod Sepiella japonica: Identification, characterisation, and expression profiling during different stages of gonadal development

Neuropeptides, Journal Year: 2024, Volume and Issue: 106, P. 102437 - 102437

Published: May 9, 2024

Language: Английский

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