ArticleThe Journal of general physiology2008
Modular design of Cys-loop ligand-gated ion channels: functional 5-HT3 and GABA rho1 receptors lacking the large cytoplasmic M3M4 loop.
Article in The Journal of general physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
76 citing papers in PubMed, 119 citations in OpenAlex.
- Intracellular regulation of a serotonin-gated ion channel links receptor trafficking to memory.iScience · 2026Article
- Structure of a pH-sensitive pentameric ligand-gated ion channel from the Sarcoptes scabies mite.Nature communications · 2026Article
- RIC-3 Interacts Directly with the 5-HTbioRxiv : the preprint server for biology · 2026Article
- Structural insights into GABANature communications · 2024Article
- Binding motif for RIC-3 chaperon protein in serotonin type 3A receptors.The Journal of general physiology · 2023Article
- 5-HTACS chemical neuroscience · 2022Article
- Speculation on How RIC-3 and Other Chaperones Facilitate α7 Nicotinic Receptor Folding and Assembly.Molecules (Basel, Switzerland) · 2022Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Megabodies expand the nanobody toolkit for protein structure determination by single-particle cryo-EM.Nature methods · 2021Article
- Mobility of Lower MA-Helices for Ion Conduction through Lateral Portals in 5-HTBiophysical journal · 2020Article
- Analysis of Modulation of theMolecular pharmacology · 2020Article
- Site-specific effects of neurosteroids on GABAeLife · 2020Article
- Differential Coassembly of α1-GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Modulation of glycine receptor single-channel conductance by intracellular phosphorylation.Scientific reports · 2020Article
- Bupropion Inhibits Serotonin Type 3AB Heteromeric Channels at Clinically Relevant Concentrations.Molecular pharmacology · 2020Article
- Delineating the Site of Interaction of the 5-HTBiophysical journal · 2020Article
- Triple arginines as molecular determinants for pentameric assembly of the intracellular domain of 5-HTThe Journal of general physiology · 2019Article
- Multiple functional neurosteroid binding sites on GABAA receptors.PLoS biology · 2019Article
- Downregulation of 5-hydroxytryptamine receptor 3A expression exerts an anticancer activity against cell growth in colorectal carcinoma cellsOncology letters · 2018Article
- Structure of a human synaptic GABANature · 2018Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cys-loop receptor neurotransmitter-gated ion channels are pentameric assemblies of subunits that contain three domains: extracellular, transmembrane, and intracellular. The extracellular domain forms the agonist binding site. The transmembrane domain forms the ion channel. The cytoplasmic domain is involved in trafficking, localization, and modulation by cytoplasmic second messenger systems but its role in channel assembly and function is poorly understood and little is known about its structure. The intracellular domain is formed by the large (>100 residues) loop between the alpha-helical M3 and M4 transmembrane segments. Putative prokaryotic Cys-loop homologues lack a large M3M4 loop. We replaced the complete M3M4 loop (115 amino acids) in the 5-hydroxytryptamine type 3A (5-HT(3A)) subunit with a heptapeptide from the prokaryotic homologue from Gloeobacter violaceus. The macroscopic electrophysiological and pharmacological characteristics of the homomeric 5-HT(3A)-glvM3M4 receptors were comparable to 5-HT(3A) wild type. The channels remained cation-selective but the 5-HT(3A)-glvM3M4 single channel conductance was 43.5 pS as compared with the subpicosiemens wild-type conductance. Coexpression of hRIC-3, a protein that modulates expression of 5-HT(3) and acetylcholine receptors, significantly attenuated 5-HT-induced currents with wild-type 5-HT(3A) but not 5-HT(3A)-glvM3M4 receptors. A similar deletion of the M3M4 loop in the anion-selective GABA-rho1 receptor yielded functional, GABA-activated, anion-selective channels. These results imply that the M3M4 loop is not essential for receptor assembly and function and suggest that the cytoplasmic domain may fold as an independent module from the transmembrane and extracellular domains.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.