Cited by Molecular tuning of sea anemone stinging

Acid-sensing ion channels and downstream signalling in cancer cells: is there a mechanistic link? DOI

Stefan Gründer,

Jakob Vanek,

Karolos‐Philippos Pissas

et al.

Pflügers Archiv - European Journal of Physiology, Journal Year: 2024, Volume and Issue: 476(4), P. 659 - 672

Published: Jan. 4, 2024

Abstract It is increasingly appreciated that the acidic microenvironment of a tumour contributes to its evolution and clinical outcomes. However, our understanding mechanisms by which cells detect acidosis signalling cascades it induces still limited. Acid-sensing ion channels (ASICs) are sensitive receptors for protons; therefore, they also candidates proton sensors in cells. Although non-transformed tissue, their expression mainly restricted neurons, an increasing number studies have reported ectopic ASICs not only brain cancer but different carcinomas, such as breast pancreatic cancer. because best known desensitizing ionotropic mediate rapid transient signalling, how trigger intracellular well understood. In this review, we introduce tumours functional properties ASICs, point out some conceptual problems, summarize roles cancers, highlight open questions on action Finally, propose guidelines keep ASIC research solid ground.

Language: Английский

Citations

Structural basis for excitatory neuropeptide signaling DOI

Valeria Kalienkova, Mowgli Dandamudi, Cristina Paulino

et al.

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

Citations

Peripheral and central employment of acid-sensing ion channels during early bilaterian evolution DOI

Josep Martí‐Solans, Aina Børve, Paul Bump

et al.

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

Published: Feb. 23, 2023

Nervous systems are endowed with rapid chemosensation and intercellular signaling by ligand-gated ion channels (LGICs). While a complex, bilaterally symmetrical nervous system is major innovation of bilaterian animals, the employment specific LGICs during early evolution poorly understood. We therefore questioned animals’ acid-sensing (ASICs), that mediate fast excitatory responses to decreases in extracellular pH vertebrate neurons. Our phylogenetic analysis identified an earlier emergence ASICs from overarching DEG/ENaC (degenerin/epithelial sodium channel) superfamily than previously thought suggests were innovation. broad examination ASIC gene expression biophysical function each lineage Xenacoelomorpha, Protostomia, Deuterostomia earliest probably expressed periphery, before being incorporated into brain as it emerged independently certain deuterostomes xenacoelomorphs. The loss peripheral cells Ecdysozoa after they separated other protostomes likely explains their ASICs, thus absence model organisms Drosophila Caenorhabditis elegans . Thus, our use diverse bilaterians investigation LGIC offers unique hypothesis on evolution.

Language: Английский

Citations

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

Wassim Elkhatib, Luis Alfonso Yañez Guerra, Tatiana D. Mayorova

et al.

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

Citations

Global analysis of ligand-gated ion channel conservation across Platyhelminthes DOI

Víctor Hugo Caña‐Bozada,

Ahmed A Z Dawoud,

I. Cruz

et al.

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

Citations

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

Josep Martí‐Solans, Aina Børve,

Line Vevle

et al.

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

Citations

A conserved peptide-binding pocket in HyNaC/ASIC ion channels DOI

Audrey Ortega-Ramírez, Simone Albani,

Michèle Bachmann

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(41)

Published: Oct. 4, 2024

The only known peptide-gated ion channels—FaNaCs/WaNaCs and HyNaCs—belong to different clades of the DEG/ENaC family. FaNaCs are activated by short neuropeptide FMRFamide, HyNaCs Hydra RFamides, which not evolutionarily related FMRFamide. FMRFamide-binding site in was recently identified a cleft atop large extracellular domain. However, this is conserved HyNaCs. Here, we combined molecular modeling site-directed mutagenesis putative binding pocket for Hydra-RFamides domain heterotrimeric HyNaC2/3/5. This localizes one three subunit interfaces, indicating that trimeric channel binds single peptide ligand. We engineered an unnatural amino acid at entrance, allowed covalent tethering RFamide channel, thereby trapping open conformation. same region as acidic acid-sensing channels (ASICs), ligands. less acidic, both electrostatic hydrophobic interactions contribute binding. Collectively, our results reveal ligand-binding ASICs indicate independent evolution peptide-binding cavities two subgroups channels.

Language: Английский

Citations

The diverse functions of the DEG/ENaC family: linking genetic and physiological insights DOI

Eva Kaulich,

Laura J Grundy,

William R Schafer

et al.

The Journal of Physiology, Journal Year: 2022, Volume and Issue: 601(9), P. 1521 - 1542

Published: Oct. 31, 2022

The DEG/ENaC family of ion channels was defined based on the sequence similarity between degenerins (DEG) from nematode Caenorhabditis elegans and subunits mammalian epithelial sodium channel (ENaC), also includes a diverse array non-voltage-gated cation across animal phyla, including acid-sensing (ASICs) Drosophila pickpockets. ENaCs ASICs have wide ranging medical importance; for example, play an important role in respiratory renal function, ischaemia inflammatory pain, as well being implicated memory learning. Electrophysiological approaches, both vitro vivo, played essential establishing physiological properties this family, identifying modulators implicating them extensive range cellular functions, mechanosensation, acid sensation synaptic modulation. Likewise, genetic studies invertebrates vertebrates linking our understanding to function at whole animal/behavioural level. Drawing together evidence is furthering precise roles channels, with diversity among members allowing comparative dissect molecular basis these functions.

Language: Английский

Citations

Molecular tuning of sea anemone stinging DOI

Lily S He,

Yujia Qi,

Corey AH Allard

et al.

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

Published: July 5, 2023

Jellyfish and sea anemones fire single-use, venom-covered barbs to immobilize prey or predators. We previously showed that the anemone Nematostella vectensis uses a specialized voltage-gated calcium (CaV) channel trigger stinging in response synergistic prey-derived chemicals touch (Weir et al., 2020). Here, we use experiments theory find behavior is suited distinct ecological niches. burrowing uniquely strong CaV inactivation for precise control of predatory stinging. In contrast, related Exaiptasia diaphana inhabits exposed environments support photosynthetic endosymbionts. Consistent with its niche, indiscriminately stings defense expresses splice variant confers weak inactivation. Chimeric analyses reveal CaVβ subunit adaptations regulate inactivation, suggesting an evolutionary tuning mechanism behavior. These findings demonstrate how functional specialization ion structure contributes organismal

Language: Английский

Citations

Adaptive Cellular Radiations and the Genetic Mechanisms Underlying Animal Nervous System Diversification DOI

Jenks Hehmeyer, Flora Plessier, Heather Marlow

et al.

Annual Review of Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 40(1), P. 407 - 425

Published: July 25, 2024

In animals, the nervous system evolved as primary interface between multicellular organisms and environment. As became larger more complex, functions of expanded to include modulation coordination individual responsive cells via paracrine synaptic well monitor maintain organism's own internal This was initially accomplished signaling eventually through assembly multicell circuits in some lineages. Cells with similar centralized systems have independently arisen several We highlight molecular mechanisms that underlie parallel diversifications system.

Language: Английский

Citations