Genes affecting the activity of nicotinic receptors involved in Caenorhabditis elegans egg-laying behavior.
Egg-laying behavior in Caenorhabditis elegans is regulated by multiple neurotransmitters, including acetylcholine and serotonin. Agonists of nicotinic acetylcholine receptors such as nicotine and levamisole stimulate egg laying; however, the genetic and molecular basis for cholinergic neurotransmission in the egg-laying circuitry is not well understood. Here we describe the egg-laying phenotypes of eight levamisole resistance genes, which affect the activity of levamisole-sensitive nicotinic receptors in nematodes. Seven of these genes, including the nicotinic receptor subunit genes unc-29, unc-38, and lev-1, were essential for the stimulation of egg laying by levamisole, though they had only subtle effects on egg-laying behavior in the absence of drug. Thus, these genes appear to encode components of a nicotinic receptor that can promote egg laying but is not necessary for egg-laying muscle contraction. Since the levamisole-receptor mutants responded to other cholinergic drugs, other acetylcholine receptors are likely to function in parallel with the levamisole-sensitive receptors to mediate cholinergic neurotransmission in the egg-laying circuitry. In addition, since expression of functional unc-29 in muscle cells restored levamisole sensitivity under some but not all conditions, both neuronal and muscle cell UNC-29 receptors are likely to contribute to the regulation of egg-laying behavior. Mutations in one levamisole receptor gene, unc-38, also conferred both hypersensitivity and reduced peak response to serotonin; thus nicotinic receptors may play a role in regulating serotonin response pathways in the egg-laying neuromusculature.
Kim
J
J
Division of Biology, University of California, San Diego, California 92093-0349, USA.
Poole
D S
DS
Waggoner
L E
LE
Kempf
A
A
Ramirez
D S
DS
Treschow
P A
PA
Schafer
W R
WR
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D017238:Genes, Helminth / Q000502:physiology*; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D007978:Levamisole / Q000378:metabolism*; D010058:Oviposition / Q000502:physiology*; D010641:Phenotype; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
D015801:Helminth Proteins; D011978:Receptors, Nicotinic; D007978:Levamisole; D012701:Serotonin