The Caenorhabditis elegans unc-63 gene encodes a levamisole-sensitive nicotinic acetylcholine receptor alpha subunit.
The anthelmintic drug levamisole causes hypercontraction of body wall muscles and lethality in nematode worms. In the nematode Caenorhabditis elegans, a genetic screen for levamisole resistance has identified 12 genes, three of which (unc-38, unc-29, and lev-1) encode nicotinic acetylcholine receptor (nAChR) subunits. Here we describe the molecular and functional characterization of another levamisole-resistant gene, unc-63, encoding a nAChR alpha subunit with a predicted amino acid sequence most similar to that of UNC-38. Like UNC-38 and UNC-29, UNC-63 is expressed in body wall muscles. In addition, UNC-63 is expressed in vulval muscles and neurons. We also show that LEV-1 is expressed in body wall muscle, thus overlapping the cellular localization of UNC-63, UNC-38, and UNC-29 and suggesting possible association in vivo. This is supported by electrophysiological studies on body wall muscle, which demonstrate that a levamisole-sensitive nAChR present at the C. elegans neuromuscular junction requires both UNC-63 and LEV-1 subunits. Thus, at least four subunits, two alpha types (UNC-38 and UNC-63) and two non-alpha types (UNC-29 and LEV-1), can contribute to levamisole-sensitive muscle nAChRs in nematodes.
Medical Research Council Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, United Kingdom.
Emmanuel
E
Culetto
Howard A
HA
Baylis
Janet E
JE
Richmond
Andrew K
AK
Jones
John T
JT
Fleming
Michael D
MD
Squire
James A
JA
Lewis
David B
DB
Sattelle
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000502:physiology*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004594:Electrophysiology; D007978:Levamisole / Q000494:pharmacology*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D010455:Peptides / Q000737:chemistry; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000502:physiology*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D019076:Transgenes
D000969:Antinematodal Agents; D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D010455:Peptides; D011978:Receptors, Nicotinic; C493164:Unc-63 protein, C elegans; D007978:Levamisole