The Caenorhabditis elegans lev-8 gene encodes a novel type of nicotinic acetylcholine receptor alpha subunit.
We have cloned Caenorhabditis elegans lev-8 and demonstrated that it encodes a novel nicotinic acetylcholine receptor (nAChR) subunit (previously designated ACR-13), which has functional roles in body wall and uterine muscles as part of a levamisole-sensitive receptor. LEV-8 is an alpha subunit and is the first to be described from the ACR-8-like group, a new class of nAChR with atypical acetylcholine-binding site (loop C) and channel-lining motifs. A single base pair change in the first intron of lev-8 in lev-8(x15) mutants leads to alternative splicing and the introduction of a premature stop codon. lev-8(x15) worms are partially resistant to levamisole-induced egg laying and paralysis, phenotypes rescued by expression of the wild-type gene. lev-8(x15) worms also show reduced rates of pharyngeal pumping. Electrophysiological recordings from body wall muscle show that currents recorded in response to levamisole have reduced amplitude in lev-8(x15) compared with wild-type animals. Consistent with these phenotypic observations, green fluorescent protein fused to LEV-8 is expressed in body wall and uterine muscle, motor neurons and epithelial-derived socket cells. Thus, LEV-8 is a levamisole receptor subunit and exhibits the most diverse expression pattern of any invertebrate nAChR subunit studied to date.
Towers
Paula R
PR
MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, Oxford, UK.
Edwards
Ben
B
Richmond
Janet E
JE
Sattelle
David B
DB
D000200:Action Potentials / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D000969:Antinematodal Agents / Q000494:pharmacology; D001522:Behavior, Animal; D015152:Blotting, Northern / Q000379:methods; D049628:Body Size / Q000235:genetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D003001:Cloning, Molecular / Q000379:methods; D004594:Electrophysiology / Q000379:methods; D004847:Epithelial Cells / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology; D015870:Gene Expression; D023281:Genomics / Q000379:methods; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007978:Levamisole / Q000494:pharmacology; D009068:Movement / Q000187:drug effects / Q000502:physiology; D009132:Muscles / Q000187:drug effects / Q000502:physiology; D009154:Mutation; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010614:Pharynx / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D012098:Reproduction / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D019076:Transgenes
D000969:Antinematodal Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D029742:Caenorhabditis elegans Proteins; D018722:Nicotinic Agonists; D011725:Pyridines; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D049452:Green Fluorescent Proteins; D007978:Levamisole; D009538:Nicotine; C082748:epibatidine