Cholinergic receptor mutants of the nematode Caenorhabditis elegans.
Potential acetylcholine receptor (AChR) mutants of the nematode are selectable by resistance to the neurotoxic drug levamisole, a probable cholinergic agonist. To determine which mutants may have achieved resistance through loss of levamisole receptor function, we have assayed mutant extracts for specific 3H-meta-aminolevamisole binding activity in the presence and absence of mecamylamine. We find that mutants in 3 of the 7 genes associated with extreme levamisole resistance are obviously deficient in saturable specific 3H-meta-aminolevamisole binding activity. Mutants of the 4 other genes have abnormal binding activities that fail to undergo the apparent allosteric activation of saturable specific 3H-meta-aminolevamisole binding activity caused by mecamylamine. Thus, all 7 genes appear to be required to produce a fully functional levamisole receptor. Mutants of several other genes associated only with partial resistance to levamisole have at least grossly normal receptor binding activities.
Lewis
J A
JA
Department of Biological Sciences, University of Missouri, Columbia 65211.
Elmer
J S
JS
Skimming
J
J
McLafferty
S
S
Fleming
J
J
McGee
T
T
D000818:Animals; D002107:Caenorhabditis / Q000235:genetics* / Q000502:physiology; D004351:Drug Resistance; D005796:Genes; D007978:Levamisole / Q000494:pharmacology; D009154:Mutation; D011950:Receptors, Cholinergic / Q000235:genetics* / Q000378:metabolism
D011950:Receptors, Cholinergic; D007978:Levamisole