A chemogenetic technology using insect Ionotropic Receptors to stimulate target cell populations in the mammalian brain
Chemogenetics uses artificially-engineered proteins to modify the activity of cells, notably neurons, in response to small molecules. Although a common set of chemogenetic tools are the G protein-coupled receptor-based DREADDs, there has been great hope for ligand-gated, ion channel-type chemogeneti...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Neuroscience Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0168010224001366 |
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| author | Yoshio Iguchi Richard Benton Kazuto Kobayashi |
| author_facet | Yoshio Iguchi Richard Benton Kazuto Kobayashi |
| author_sort | Yoshio Iguchi |
| collection | DOAJ |
| description | Chemogenetics uses artificially-engineered proteins to modify the activity of cells, notably neurons, in response to small molecules. Although a common set of chemogenetic tools are the G protein-coupled receptor-based DREADDs, there has been great hope for ligand-gated, ion channel-type chemogenetic tools that directly impact neuronal excitability. We have devised such a technology by exploiting insect Ionotropic Receptors (IRs), a highly divergent subfamily of ionotropic glutamate receptors that evolved to detect diverse environmental chemicals. Here, we review a series of studies developing and applying this “IR-mediated neuronal activation” (IRNA) technology with the Drosophila melanogaster IR84a/IR8a complex, which detects phenyl-containing ligands. We also discuss how variants of IRNA could be produced by modifying the composition of the IR complex, using natural or engineered subunits, which would enable artificial activation of different cell populations in the brain in response to distinct chemicals. |
| format | Article |
| id | doaj-art-59d2acaf7f914e29b0db593a2b7be035 |
| institution | OA Journals |
| issn | 0168-0102 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neuroscience Research |
| spelling | doaj-art-59d2acaf7f914e29b0db593a2b7be0352025-08-20T02:30:15ZengElsevierNeuroscience Research0168-01022025-05-01214566110.1016/j.neures.2024.11.003A chemogenetic technology using insect Ionotropic Receptors to stimulate target cell populations in the mammalian brainYoshio Iguchi0Richard Benton1Kazuto Kobayashi2Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, JapanCenter for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne CH-1015, SwitzerlandDepartment of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Japan; Corresponding author.Chemogenetics uses artificially-engineered proteins to modify the activity of cells, notably neurons, in response to small molecules. Although a common set of chemogenetic tools are the G protein-coupled receptor-based DREADDs, there has been great hope for ligand-gated, ion channel-type chemogenetic tools that directly impact neuronal excitability. We have devised such a technology by exploiting insect Ionotropic Receptors (IRs), a highly divergent subfamily of ionotropic glutamate receptors that evolved to detect diverse environmental chemicals. Here, we review a series of studies developing and applying this “IR-mediated neuronal activation” (IRNA) technology with the Drosophila melanogaster IR84a/IR8a complex, which detects phenyl-containing ligands. We also discuss how variants of IRNA could be produced by modifying the composition of the IR complex, using natural or engineered subunits, which would enable artificial activation of different cell populations in the brain in response to distinct chemicals.http://www.sciencedirect.com/science/article/pii/S0168010224001366Chemogenetic toolIonotropic ReceptorsIR84a/IR8a complexPhenylacetic acidProdrug system |
| spellingShingle | Yoshio Iguchi Richard Benton Kazuto Kobayashi A chemogenetic technology using insect Ionotropic Receptors to stimulate target cell populations in the mammalian brain Neuroscience Research Chemogenetic tool Ionotropic Receptors IR84a/IR8a complex Phenylacetic acid Prodrug system |
| title | A chemogenetic technology using insect Ionotropic Receptors to stimulate target cell populations in the mammalian brain |
| title_full | A chemogenetic technology using insect Ionotropic Receptors to stimulate target cell populations in the mammalian brain |
| title_fullStr | A chemogenetic technology using insect Ionotropic Receptors to stimulate target cell populations in the mammalian brain |
| title_full_unstemmed | A chemogenetic technology using insect Ionotropic Receptors to stimulate target cell populations in the mammalian brain |
| title_short | A chemogenetic technology using insect Ionotropic Receptors to stimulate target cell populations in the mammalian brain |
| title_sort | chemogenetic technology using insect ionotropic receptors to stimulate target cell populations in the mammalian brain |
| topic | Chemogenetic tool Ionotropic Receptors IR84a/IR8a complex Phenylacetic acid Prodrug system |
| url | http://www.sciencedirect.com/science/article/pii/S0168010224001366 |
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