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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-12

AUTHORS

Aude S Peden, Patrick Mac, You-Jun Fei, Cecilia Castro, Guoliang Jiang, Kenneth J Murfitt, Eric A Miska, Julian L Griffin, Vadivel Ganapathy, Erik M Jorgensen

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. More... »

PAGES

1794-1801

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nn.3575

DOI

http://dx.doi.org/10.1038/nn.3575

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016636979

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24212673


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