Betaine acts on a ligand-gated ion channel in the nervous system of the nematode C. elegans
| Autor: | Erik M. Jorgensen, Vadivel Ganapathy, Guoliang Jiang, Kenneth J. Murfitt, Aude S. Peden, Eric A. Miska, Julian L. Griffin, You Jun Fei, Patrick Mac, Cecilia Castro |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
1702 Cognitive Sciences
Receptors Nicotinic Betaine transporter Nervous System Membrane Potentials Animals Genetically Modified chemistry.chemical_compound 0302 clinical medicine Betaine Body Size Caenorhabditis elegans chemistry.chemical_classification 0303 health sciences Neurotransmitter Agents biology General Neuroscience Antinematodal Agents Gene Expression Regulation Developmental Amino acid Biochemistry Osmolyte Larva C. elegans Ligand-gated ion channel Signal transduction phospholipase Cβ Ion Channel Gating Mechanoreceptors Allosteric modulator betaine transporter Green Fluorescent Proteins Article 03 medical and health sciences Animals Humans Caenorhabditis elegans Proteins 030304 developmental biology ACR-23 egl-8 Neurology & Neurosurgery Dose-Response Relationship Drug Ligand-Gated Ion Channels biology.organism_classification SNF-3 betaine receptor chemistry 1701 Psychology Mutation 1109 Neurosciences 030217 neurology & neurosurgery |
| Zdroj: | Nature neuroscience |
| ISSN: | 1546-1726 1097-6256 |
| Popis: | Prior to the advent of synthetic nematocides, natural products such as seaweed were used to control nematode infestations. The nematocidal agent in seaweed is betaine, an amino acid that functions as an osmolyte and methyl donor. However, the molecular mechanisms of betaine toxicity are unknown. We identified the betaine transporter SNF-3 and the betaine receptor ACR-23 in the nematode C. elegans. Mutating snf-3 in a sensitized background caused the worms to be hypercontracted and paralyzed, presumably as a result of excess extracellular betaine. These behavioral defects were suppressed by mutations in acr-23, which encodes a ligand-gated cation channel of the cys-loop family. ACR-23 was activated by betaine and functioned in the mechanosensory neurons to maintain basal levels of locomotion. However, overactivation of the receptor by excess betaine or by the allosteric modulator monepantel resulted in hypercontraction and death of the nematode. Thus, monepantel targets a betaine signaling pathway in nematodes. |
| Databáze: | OpenAIRE |
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