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

Mutations in the unc-9 gene of the nematode Caenorhabditis elegans cau se abnormal forward locomotion and an egg-retention phenotype. unc-9 m utations also reduce the worms' sensitivity to avermectin and block a form of hypersensitivity to volatile anesthetics. We report here the c loning and molecular characterization of unc-9 and show that it encode s a member of the OPUS family of proteins that is 56% identical to ano ther OPUS protein, UNC-7. It is significant that unc-9 mutants share a ll phenotypes with unc-7 mutants. Mutants in another gene, unc-124, al so 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 implica ted 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 cou ld form a hydrophilic pore. We also show that alteration of highly con served proline residues in UNC-9 reads to a cold sensitivity that like ly affects a step in protein expression rather than function. Finally, we speculate on the basis of the avermectin resistance and anesthetic response phenotypes.