ArticleThe Journal of biological chemistry2013
An engineered glutamate-gated chloride (GluCl) channel for sensitive, consistent neuronal silencing by ivermectin.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- The Future of Chemogenetics for the Treatment of Spasticity.Molecular diagnosis & therapy · 2025Review
- Preliminary study on toxicological mechanism of golden cuttlefish (Sepia esculenta) larvae exposed to cd.BMC genomics · 2023Article
- Chemogenetics of cell surface receptors: beyond genetic and pharmacological approaches.RSC chemical biology · 2022Review
- Chemogenetics: Beyond Lesions and Electrodes.Neurosurgery · 2021Review
- Ion channel engineering for modulation and de novo generation of electrical excitability.Current opinion in biotechnology · 2019Review
- Bringing balance to the force-regulatable gene therapy for epilepsy.Gene therapy · 2019Article
- Electromagnetic Regulation of Cell Activity.Cold Spring Harbor perspectives in medicine · 2019Review
- Designer receptor technology for the treatment of epilepsy.EBioMedicine · 2019Review
- Ultrapotent chemogenetics for research and potential clinical applications.Science (New York, N.Y.) · 2019Article
- Biochemical autoregulatory gene therapy for focal epilepsy.Nature medicine · 2018Article
- Chemogenetic Tools for Causal Cellular and Neuronal Biology.Physiological reviews · 2018Review
- Applications of optogenetic and chemogenetic methods to seizure circuits: Where to go next?Journal of neuroscience research · 2017Review
- Chemogenetic management of neuropathic pain.Brain : a journal of neurology · 2017Article
- Using an engineered glutamate-gated chloride channel to silence sensory neurons and treat neuropathic pain at the source.Brain : a journal of neurology · 2017Article
- Review
- Trapping of ivermectin by a pentameric ligand-gated ion channel upon open-to-closed isomerization.Scientific reports · 2017Article
- Mutational Analysis at Intersubunit Interfaces of an Anionic Glutamate Receptor Reveals a Key Interaction Important for Channel Gating by Ivermectin.Frontiers in molecular neuroscience · 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
- Subunit stoichiometry and arrangement in a heteromeric glutamate-gated chloride channel.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The Validation of Nematode-Specific Acetylcholine-Gated Chloride Channels as Potential Anthelmintic Drug Targets.PloS one · 2015Article
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 2 countries.
Funding
Abstract
A modified invertebrate glutamate-gated Cl(-) channel (GluCl αβ) was previously employed to allow pharmacologically induced silencing of electrical activity in CNS neurons upon exposure to the anthelmintic drug ivermectin (IVM). Usefulness of the previous receptor was limited by 1) the high concentration of IVM necessary to elicit a consistent silencing phenotype, raising concern about potential side effects, and 2) the variable extent of neuronal spike suppression, due to variations in the co-expression levels of the fluorescent protein-tagged α and β subunits. To address these issues, mutant receptors generated via rational protein engineering strategies were examined for improvement. Introduction of a gain-of-function mutation (L9'F) in the second transmembrane domain of the α subunit appears to facilitate β subunit incorporation and substantially increase heteromeric GluCl αβ sensitivity to IVM. Removal of an arginine-based endoplasmic reticulum retention motif (RSR mutated to AAA) from the intracellular loop of the β subunit further promotes heteromeric expression at the plasma membrane possibly by preventing endoplasmic reticulum-associated degradation of the β subunit rather than simply reducing endoplasmic reticulum retention. A monomeric XFP (mXFP) mutation that prevents fluorescent protein dimerization complements the mutant channel effects. Expression of the newly engineered GluCl opt α-mXFP L9'F + opt β-mXFP Y182F RSR_AAA receptor in dissociated neuronal cultures markedly increases conductance and reduces variability in spike suppression at 1 nm IVM. This receptor, named "GluClv2.0," is an improved tool for IVM-induced silencing.
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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.