Betaine acts on a ligand-gated ion channel in the nervous system of the nematode C. elegans.

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Bibliographic Details
Title:	Betaine acts on a ligand-gated ion channel in the nervous system of the nematode C. elegans.
Authors:	Peden, Aude S, Mac, Patrick, Fei, You-Jun, Castro, Cecilia, Jiang, Guoliang, Murfitt, Kenneth J, Miska, Eric A, Griffin, Julian L, Ganapathy, Vadivel, Jorgensen, Erik M
Source:	Nature Neuroscience. Dec2013, Vol. 16 Issue 12, p1794-1801. 8p.
Subjects:	Betaine, Alkaloids, Marine algae, Caenorhabditis elegans, Ion channels, Amino acids
Abstract:	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. [ABSTRACT FROM AUTHOR]
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Database:	Psychology and Behavioral Sciences Collection

Description
Abstract:	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. [ABSTRACT FROM AUTHOR]
ISSN:	10976256
DOI:	10.1038/nn.3575