ArticlePloS one2016
Evolution of Pentameric Ligand-Gated Ion Channels: Pro-Loop Receptors.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 111 citations in OpenAlex.
- Functional Analysis of Ligand-Gated Chloride Channels in a Cnidarian Sheds Light on the Evolution of Inhibitory Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- An atomic interaction conserved for over 600 million years gates inhibitory neurotransmission.bioRxiv : the preprint server for biology · 2026Article
- Calcium stabilizes the flexible N-terminal domain of the bacterial ion channel DeCLIC.Journal of structural biology: X · 2025Article
- Asymmetric gating of a homopentameric ion channel GLIC revealed by cryo-EM.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structural Determinants of Oxantel Analogs Reveal Modulatory Selectivity of α3β2 and α4β2 Neuronal Nicotinic Acetylcholine Receptors.ACS omega · 2025Article
- Electrically silent mutants unravel the mechanism of binding-gating coupling in Cys-loop receptors.Science advances · 2024Article
- Structure of tetrameric forms of the serotonin-gated 5-HT3The EMBO journal · 2024Article
- Key role of the TM2-TM3 loop in calcium potentiation of the α9α10 nicotinic acetylcholine receptor.Cellular and molecular life sciences : CMLS · 2024Article
- Channels of Evolution: Unveiling Evolutionary Patterns in Diatom CaPlants (Basel, Switzerland) · 2024Article
- Short-chain mono-carboxylates as negative modulators of allosteric transitions in Gloeobacter violaceus ligand-gated ion channel, and impact of a pre-β5 strand (Loop Ω) double mutation on crotonate, not butyrate effect.Physiological reports · 2024Article
- Phenols and GABAFrontiers in pharmacology · 2024Review
- C5 methylation confers accessibility, stability and selectivity to picrotoxinin.Nature communications · 2023Article
- GABACell biology and toxicology · 2023Article
- Review
- The diverse family of Cys-loop receptors inBiophysical reviews · 2023Review
- A new family of glutamate-gated chloride channels in parasitic sea louse Caligus rogercresseyi: A subunit refractory to activation by ivermectin is dominant in heteromeric assemblies.PLoS pathogens · 2023Article
- Phenotypic Profiling of Macrocyclic Lactones on ParasiticAntimicrobial agents and chemotherapy · 2023Article
- Schistosomes contain divergent ligand-gated ion channels with an atypical Cys-loop motif.microPublication biology · 2023Article
- Biophysical characterization of calcium-binding and modulatory-domain dynamics in a pentameric ligand-gated ion channel.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Expression of Mutant Glycine Receptors inMembranes · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pentameric ligand-gated ion channels (pLGICs) are ubiquitous neurotransmitter receptors in Bilateria, with a small number of known prokaryotic homologues. Here we describe a new inventory and phylogenetic analysis of pLGIC genes across all kingdoms of life. Our main finding is a set of pLGIC genes in unicellular eukaryotes, some of which are metazoan-like Cys-loop receptors, and others devoid of Cys-loop cysteines, like their prokaryotic relatives. A number of such "Cys-less" receptors also appears in invertebrate metazoans. Together, those findings draw a new distribution of pLGICs in eukaryotes. A broader distribution of prokaryotic channels also emerges, including a major new archaeal taxon, Thaumarchaeota. More generally, pLGICs now appear nearly ubiquitous in major taxonomic groups except multicellular plants and fungi. However, pLGICs are sparsely present in unicellular taxa, suggesting a high rate of gene loss and a non-essential character, contrasting with their essential role as synaptic receptors of the bilaterian nervous system. Multiple alignments of these highly divergent sequences reveal a small number of conserved residues clustered at the interface between the extracellular and transmembrane domains. Only the "Cys-loop" proline is absolutely conserved, suggesting the more fitting name "Pro loop" for that motif, and "Pro-loop receptors" for the superfamily. The infered molecular phylogeny shows a Cys-loop and a Cys-less clade in eukaryotes, both containing metazoans and unicellular members. This suggests new hypotheses on the evolutionary history of the superfamily, such as a possible origin of the Cys-loop cysteines in an ancient unicellular eukaryote. Deeper phylogenetic relationships remain uncertain, particularly around the split between bacteria, archaea, and eukaryotes.
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