ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
The role of intracellular linkers in gating and desensitization of human pentameric ligand-gated ion channels.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Human GlyRα2 pore dynamics in gating and inhibition.Structure (London, England : 1993) · 2026Article
- RIC-3 Interacts Directly with the 5-HTbioRxiv : the preprint server for biology · 2026Article
- Gating mechanism of the human α1β GlyR by glycine.Structure (London, England : 1993) · 2024Article
- Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy.International journal of molecular sciences · 2022Article
- Acidic pH reduces agonist efficacy and responses to synaptic-like glycine applications in zebrafish α1 and rat α1β recombinant glycine receptors.The Journal of physiology · 2022Article
- Signal transduction through Cys-loop receptors is mediated by the nonspecific bumping of closely apposed domains.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A novel fast-channel myasthenia caused by mutation in β subunit of AChR reveals subunit-specific contribution of the intracellular M1-M2 linker to channel gating.Experimental neurology · 2020Article
- Mechanisms of activation and desensitization of full-length glycine receptor in lipid nanodiscs.Nature communications · 2020Article
- A Novel Glycine Receptor Variant with Startle Disease Affects Syndapin I and Glycinergic Inhibition.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Cryo-EM structures of a lipid-sensitive pentameric ligand-gated ion channel embedded in a phosphatidylcholine-only bilayer.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Triple arginines as molecular determinants for pentameric assembly of the intracellular domain of 5-HTThe Journal of general physiology · 2019Article
- Cryo-EM structure of the human α1β3γ2 GABANature · 2019Article
- The dual-gate model for pentameric ligand-gated ion channels activation and desensitization.The Journal of physiology · 2018Review
- 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
- Chasing the open-state structure of pentameric ligand-gated ion channels.The Journal of general physiology · 2017Article
- Identifying the elusive link between amino acid sequence and charge selectivity in pentameric ligand-gated ion channels.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Electrophysiological Signature of Homomeric and Heteromeric Glycine Receptor Channels.The Journal of biological chemistry · 2016Article
- Assessment of the expression and role of the α1-nAChR subunit in efferent cholinergic function during the development of the mammalian cochlea.Journal of neurophysiology · 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
- The Intracellular Loop of the Glycine Receptor: It's not all about the Size.Frontiers in molecular neuroscience · 2016Review
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2 authors.
Funding
Abstract
It has recently been proposed that post-translational modification of not only the M3-M4 linker but also the M1-M2 linker of pentameric ligand-gated ion channels modulates function in vivo. To estimate the involvement of the M1-M2 linker in gating and desensitization, we engineered a series of mutations to this linker of the human adult-muscle acetylcholine receptor (AChR), the α3β4 AChR and the homomeric α1 glycine receptor (GlyR). All tested M1-M2 linker mutations had little effect on the kinetics of deactivation or desensitization compared with the effects of mutations to the M2 α-helix or the extracellular M2-M3 linker. However, when the effects of mutations were assessed with 50 Hz trains of ∼1 ms pulses of saturating neurotransmitter, some mutations led to much more, and others to much less, peak-current depression than observed for the wild-type channels, suggesting that these mutations could affect the fidelity of fast synaptic transmission. Nevertheless, no mutation to this linker could mimic the irreversible loss of responsiveness reported to result from the oxidation of the M1-M2 linker cysteines of the α3 AChR subunit. We also replaced the M3-M4 linker of the α1 GlyR with much shorter peptides and found that none of these extensive changes affects channel deactivation strongly or reduces the marked variability in desensitization kinetics that characterizes the wild-type channel. However, we found that these large mutations to the M3-M4 linker can have pronounced effects on desensitization kinetics, supporting the notion that its post-translational modification could indeed modulate α1 GlyR behavior.
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