title: IRK-1 potassium channels mediate peptidergic inhibition of Caenorhabditis elegans serotonin neurons via a G(o) signaling pathway.
abstract: To identify molecular mechanisms that function in G-protein signaling, we have performed molecular genetic studies of a simple behavior of the nematode Caenorhabditis elegans, egg laying, which is driven by a pair of serotonergic neurons, the hermaphrodite-specific neurons (HSNs). The activity of the HSNs is regulated by the G(o)-coupled receptor EGL-6, which mediates inhibition of the HSNs by neuropeptides. We report here that this inhibition requires one of three inwardly rectifying K(+) channels encoded by the C. elegans genome: IRK-1. Using ChannelRhodopsin-2-mediated stimulation of HSNs, we observed roles for egl-6 and irk-1 in regulating the excitability of HSNs. Although irk-1 is required for inhibition of HSNs by EGL-6 signaling, we found that other G(o) signaling pathways that inhibit HSNs involve irk-1 little or not at all. These findings suggest that the neuropeptide receptor EGL-6 regulates the potassium channel IRK-1 via a dedicated pool of G(o) not involved in other G(o)-mediated signaling. We conclude that G-protein-coupled receptors that signal through the same G-protein in the same cell might activate distinct effectors and that specific coupling of a G-protein-coupled receptor to its effectors can be determined by factors other than its associated G-proteins.
authors.affiliation: Skirball Institute of Biomolecular Medicine, Molecular Neurobiology Program, Department of Cell Biology, New York University Langone Medical Center, New York, New York 10016, USA.
authors.forename: Lesley
authors.initials: L
authors.lastname: Emtage
authors.forename: Sonya
authors.initials: S
authors.lastname: Aziz-Zaman
authors.forename: Olivia
authors.initials: O
authors.lastname: Padovan-Merhar
authors.forename: H Robert
authors.initials: HR
authors.lastname: Horvitz
authors.forename: Christopher
authors.initials: C
authors.lastname: Fang-Yen
authors.forename: Niels
authors.initials: N
authors.lastname: Ringstad
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000502:physiology; D017173:Caenorhabditis elegans / Q000502:physiology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology*; D016678:Genome; D015640:Ion Channel Gating / Q000502:physiology; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000494:pharmacology*; D009865:Oocytes; D016133:Polymerase Chain Reaction; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000502:physiology*; D059326:Serotonergic Neurons / Q000502:physiology*; D012726:Sexual Behavior, Animal / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D009479:Neuropeptides; D024661:Potassium Channels, Inwardly Rectifying; D019206:GTP-Binding Protein alpha Subunits, Gi-Go