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MOD-1 is a serotonin-gated chloride channel that modulates locomotory behaviour in C. elegans

Nature volume 408, pages 470–475 (2000)Cite this article

Abstract

The neurotransmitter and neuromodulator serotonin (5-HT) functions by binding either to metabotropic G-protein-coupled receptors (for example, 5-HT1, 5-HT2, 5-HT4 to 5-HT7), which mediate ‘slow’ modulatory responses through numerous second messenger pathways1, or to the ionotropic 5-HT3 receptor, a non-selective cation channel that mediates ‘fast’ membrane depolarizations2. Here we report that the gene mod-1 (for modulation of locomotion defective) from the nematode Caenorhabditis elegans encodes a new type of ionotropic 5-HT receptor, a 5-HT-gated chloride channel. The predicted MOD-1 protein is similar to members of the nicotinic acetylcholine receptor family of ligand-gated ion channels, in particular to GABA (γ-aminobutyric acid)- and glycine-gated chloride channels. The MOD-1 channel has distinctive ion selectivity and pharmacological properties. The reversal potential of the MOD-1 channel is dependent on the concentration of chloride ions but not of cations. The MOD-1 channel is not blocked by calcium ions or 5-HT3a-specific antagonists but is inhibited by the metabotropic 5-HT receptor antagonists mianserin and methiothepin. mod-1 mutant animals are defective in a 5-HT-mediated experience-dependent behaviour3 and are resistant to exogenous 5-HT, confirming that MOD-1 functions as a 5-HT receptor in vivo.

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Figure 1: Phenotypic characterization and cloning of mod-1.
Figure 2: Sequence analysis of mod-1.
Figure 3: mod-1 deletion alleles caused 5-HT resistance and defects in the enhanced slowing response.
Figure 4: MOD-1 is a 5-HT-gated ion channel distinct from the 5-HT3a channel.
Figure 5: MOD-1 is a 5-HT-gated chloride channel.

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Acknowledgements

We thank N. Buttner, D. Omura and P. Reddien for suggestions concerning this manuscript; G. Moulder and R. Barstead for help in isolating the mod-1(ok103) allele; L. Liu and C. Johnson for sharing the mod-1(nr2043) allele before publication; and D. Julius for the 5-HT3a cDNA clone. This work was supported by a grant from the United States Public Health Service (H.R.H.). R.R. is supported by a Howard Hughes Medical Institute predoctoral fellowship. H.R.H. is an Investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Howard Hughes Medical Institute Department of Biology, Room 68-425, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA

    Rajesh Ranganathan & H. Robert Horvitz

  2. Department of Neurobiology, and Department of Neurology Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, Boston, 02114, Massachusetts , USA

    Stephen C. Cannon

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Correspondence to H. Robert Horvitz.

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Ranganathan, R., Cannon, S. & Horvitz, H. MOD-1 is a serotonin-gated chloride channel that modulates locomotory behaviour in C. elegans. Nature 408, 470–475 (2000). https://doi.org/10.1038/35044083

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