title: The Caenorhabditis elegans avermectin resistance and anesthetic response gene unc-9 encodes a member of a protein family implicated in electrical coupling of excitable cells.
abstract: Mutations in the unc-9 gene of the nematode Caenorhabditis elegans cause abnormal forward locomotion and an egg-retention phenotype. unc-9 mutations also reduce the worms' sensitivity to avermectin and block a form of hypersensitivity to volatile anesthetics. We report here the cloning and molecular characterization of unc-9 and show that it encodes a member of the OPUS family of proteins that is 56% identical to another OPUS protein, UNC-7. It is significant that unc-9 mutants share all phenotypes with unc-7 mutants. Mutants in another gene, unc-124, also share all tested phenotypes with unc-9 mutants, including identical locomotory and egg-laying defects, suggesting that multiple genes are required for the same biochemical function. OPUS proteins are implicated in the function of invertebrate gap junctions, and, based on a new alignment including 24 members from C. elegans, we present a refined model for the structure of OPUS proteins suggesting that oligomers could form a hydrophilic pore. We also show that alteration of highly conserved proline residues in UNC-9 leads to a cold sensitivity that likely affects a step in protein expression rather than function. Finally, we speculate on the basis of the avermectin resistance and anesthetic response phenotypes.
authors.affiliation: Department of Biology, McGill University, Montréal, Québec, Canada.
authors.forename: T M
authors.initials: TM
authors.lastname: Barnes
authors.forename: S
authors.initials: S
authors.lastname: Hekimi
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D005260:Female; D017629:Gap Junctions / Q000502:physiology; D015801:Helminth Proteins / Q000235:genetics*; D007305:Insecticide Resistance / Q000235:genetics; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000502:physiology; D009154:Mutation / Q000235:genetics; D010058:Oviposition / Q000502:physiology
chemical_list: D000777:Anesthetics; D000871:Anthelmintics; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D008565:Membrane Proteins; C109201:Unc-9 protein, C elegans; D007559:Ivermectin; C019264:avermectin