MOD-1 is a serotonin-gated chloride channel that modulates locomotory behaviour in C. elegans.
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 pathways, or to the ionotropic 5-HT3 receptor, a non-selective cation channel that mediates 'fast' membrane depolarizations. 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 (gamma-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 behaviour and are resistant to exogenous 5-HT, confirming that MOD-1 functions as a 5-HT receptor in vivo.
Ranganathan
R
R
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Cannon
S C
SC
Horvitz
H R
HR
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D002460:Cell Line; D018118:Chloride Channels / Q000235:genetics / Q000502:physiology*; D005091:Exons; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D007438:Introns; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D009154:Mutation; D018408:Patch-Clamp Techniques; D012701:Serotonin / Q000502:physiology*; D014162:Transfection; D014982:Xenopus laevis
D029742:Caenorhabditis elegans Proteins; D018118:Chloride Channels; D015801:Helminth Proteins; C417030:MOD-1 protein, C elegans; D012701:Serotonin