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

J Neurochem. 1997 Dec;69(6):2251-60. doi: 10.1046/j.1471-4159.1997.69062251.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Anesthetics / pharmacology*
  • Animals
  • Anthelmintics / pharmacology*
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins*
  • Cloning, Molecular
  • Female
  • Gap Junctions / physiology
  • Helminth Proteins / genetics*
  • Insecticide Resistance / genetics
  • Ivermectin / analogs & derivatives*
  • Ivermectin / pharmacology
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Motor Activity / physiology
  • Mutation / genetics
  • Oviposition / physiology

Substances

  • Anesthetics
  • Anthelmintics
  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Membrane Proteins
  • Unc-9 protein, C elegans
  • Ivermectin
  • avermectin