ArticlePloS one2012
Length and amino acid sequence of peptides substituted for the 5-HT3A receptor M3M4 loop may affect channel expression and desensitization.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Two residues determine nicotinic acetylcholine receptor requirement for RIC-3.Protein science : a publication of the Protein Society · 2023Article
- Binding motif for RIC-3 chaperon protein in serotonin type 3A receptors.The Journal of general physiology · 2023Article
- Speculation on How RIC-3 and Other Chaperones Facilitate α7 Nicotinic Receptor Folding and Assembly.Molecules (Basel, Switzerland) · 2022Review
- Triple arginines as molecular determinants for pentameric assembly of the intracellular domain of 5-HTThe Journal of general physiology · 2019Article
- A Missense Mutation A384P Associated with Human Hyperekplexia Reveals a Desensitization Site of Glycine Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel.Journal of neurochemistry · 2016Article
- The Thumb Domain Mediates Acid-sensing Ion Channel Desensitization.The Journal of biological chemistry · 2016Article
- Direct interaction of the resistance to inhibitors of cholinesterase type 3 protein with the serotonin receptor type 3A intracellular domain.Journal of neurochemistry · 2016Article
- Characterization of the target of ivermectin, the glutamate-gated chloride channel, from Anopheles gambiae.The Journal of experimental biology · 2015Article
- Functional Chimeras of GLIC Obtained by Adding the Intracellular Domain of Anion- and Cation-Conducting Cys-Loop Receptors.Biochemistry · 2015Article
- 5-Hydroxytryptamine (5-HT) cellular sequestration during chronic exposure delays 5-HT3 receptor resensitization due to its subsequent release.The Journal of biological chemistry · 2014Article
- An internally modulated, thermostable, pH-sensitive Cys loop receptor from the hydrothermal vent worm Alvinella pompejana.The Journal of biological chemistry · 2014Article
- The role of intracellular linkers in gating and desensitization of human pentameric ligand-gated ion channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Impact of intracellular domain flexibility upon properties of activated human 5-HT3 receptors.British journal of pharmacology · 2014Article
- The minimum M3-M4 loop length of neurotransmitter-activated pentameric receptors is critical for the structural integrity of cytoplasmic portals.The Journal of biological chemistry · 2013Article
- An outline of desensitization in pentameric ligand-gated ion channel receptors.Cellular and molecular life sciences : CMLS · 2013Review
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3 authors.
Funding
Abstract
5-HT3A receptors are pentameric neurotransmitter-gated ion channels in the Cys-loop receptor family. Each subunit contains an extracellular domain, four transmembrane segments (M1, M2, M3, M4) and a 115 residue intracellular loop between M3 and M4. In contrast, the M3M4 loop in prokaryotic homologues is <15 residues. To investigate the limits of M3M4 loop length and composition on channel function we replaced the 5-HT3A M3M4 loop with two to seven alanine residues (5-HT3A-A(n = 2-7)). Mutants were expressed in Xenopus laevis oocytes and characterized using two electrode voltage clamp recording. All mutants were functional. The 5-HT EC(50)'s were at most 5-fold greater than wild-type (WT). The desensitization rate differed significantly among the mutants. Desensitization rates for 5-HT3A-A(2), 5-HT3A-A(4), 5-HT3A-A(6), and 5-HT3A-A(7) were similar to WT. In contrast, 5-HT3A-A(3) and 5-HT3A-A(5) had desensitization rates at least an order of magnitude faster than WT. The one Ala loop construct, 5-HT3A-A(1), entered a non-functional state from which it did not recover after the first 5-HT application. These results suggest that the large M3M4 loop of eukaryotic Cys-loop channels is not required for receptor assembly or function. However, loop length and amino acid composition can effect channel expression and desensitization. We infer that the cytoplasmic ends of the M3 and M4 segments may undergo conformational changes during channel gating and desensitization and/or the loop may influence the position and mobility of these segments as they undergo gating-induced conformational changes. Altering structure or conformational mobility of the cytoplasmic ends of M3 and M4 may be the basis by which phosphorylation or protein binding to the cytoplasmic loop alters channel function.
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