Skip to main content
PMC home page
Genetics logoLink to Genetics
. 2001 Apr;157(4):1599–1610. doi: 10.1093/genetics/157.4.1599

Genes affecting the activity of nicotinic receptors involved in Caenorhabditis elegans egg-laying behavior.

J Kim 1, D S Poole 1, L E Waggoner 1, A Kempf 1, D S Ramirez 1, P A Treschow 1, W R Schafer 1
PMCID: PMC1461590  PMID: 11290716

Abstract

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.

Full Text

The Full Text of this article is available as a PDF (589.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Avery L., Horvitz H. R. Effects of starvation and neuroactive drugs on feeding in Caenorhabditis elegans. J Exp Zool. 1990 Mar;253(3):263–270. doi: 10.1002/jez.1402530305. [DOI] [PubMed] [Google Scholar]
  2. Ballivet M., Alliod C., Bertrand S., Bertrand D. Nicotinic acetylcholine receptors in the nematode Caenorhabditis elegans. J Mol Biol. 1996 May 3;258(2):261–269. doi: 10.1006/jmbi.1996.0248. [DOI] [PubMed] [Google Scholar]
  3. Baylis H. A., Matsuda K., Squire M. D., Fleming J. T., Harvey R. J., Darlison M. G., Barnard E. A., Sattelle D. B. ACR-3, a Caenorhabditis elegans nicotinic acetylcholine receptor subunit. Molecular cloning and functional expression. Receptors Channels. 1997;5(3-4):149–158. [PubMed] [Google Scholar]
  4. Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974 May;77(1):71–94. doi: 10.1093/genetics/77.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dani J. A., Heinemann S. Molecular and cellular aspects of nicotine abuse. Neuron. 1996 May;16(5):905–908. doi: 10.1016/s0896-6273(00)80112-9. [DOI] [PubMed] [Google Scholar]
  6. Desai C., Garriga G., McIntire S. L., Horvitz H. R. A genetic pathway for the development of the Caenorhabditis elegans HSN motor neurons. Nature. 1988 Dec 15;336(6200):638–646. doi: 10.1038/336638a0. [DOI] [PubMed] [Google Scholar]
  7. Duerr J. S., Frisby D. L., Gaskin J., Duke A., Asermely K., Huddleston D., Eiden L. E., Rand J. B. The cat-1 gene of Caenorhabditis elegans encodes a vesicular monoamine transporter required for specific monoamine-dependent behaviors. J Neurosci. 1999 Jan 1;19(1):72–84. doi: 10.1523/JNEUROSCI.19-01-00072.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fleming J. T., Squire M. D., Barnes T. M., Tornoe C., Matsuda K., Ahnn J., Fire A., Sulston J. E., Barnard E. A., Sattelle D. B. Caenorhabditis elegans levamisole resistance genes lev-1, unc-29, and unc-38 encode functional nicotinic acetylcholine receptor subunits. J Neurosci. 1997 Aug 1;17(15):5843–5857. doi: 10.1523/JNEUROSCI.17-15-05843.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fleming J. T., Tornoe C., Riina H. A., Coadwell J., Lewis J. A., Sattelle D. B. Acetylcholine receptor molecules of the nematode Caenorhabditis elegans. EXS. 1993;63:65–80. doi: 10.1007/978-3-0348-7265-2_4. [DOI] [PubMed] [Google Scholar]
  10. Galzi J. L., Revah F., Bessis A., Changeux J. P. Functional architecture of the nicotinic acetylcholine receptor: from electric organ to brain. Annu Rev Pharmacol Toxicol. 1991;31:37–72. doi: 10.1146/annurev.pa.31.040191.000345. [DOI] [PubMed] [Google Scholar]
  11. Harfe B. D., Fire A. Muscle and nerve-specific regulation of a novel NK-2 class homeodomain factor in Caenorhabditis elegans. Development. 1998 Feb;125(3):421–429. doi: 10.1242/dev.125.3.421. [DOI] [PubMed] [Google Scholar]
  12. Lewis J. A., Elmer J. S., Skimming J., McLafferty S., Fleming J., McGee T. Cholinergic receptor mutants of the nematode Caenorhabditis elegans. J Neurosci. 1987 Oct;7(10):3059–3071. doi: 10.1523/JNEUROSCI.07-10-03059.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lewis J. A., Wu C. H., Berg H., Levine J. H. The genetics of levamisole resistance in the nematode Caenorhabditis elegans. Genetics. 1980 Aug;95(4):905–928. doi: 10.1093/genetics/95.4.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lewis J. A., Wu C. H., Levine J. H., Berg H. Levamisole-resistant mutants of the nematode Caenorhabditis elegans appear to lack pharmacological acetylcholine receptors. Neuroscience. 1980;5(6):967–989. doi: 10.1016/0306-4522(80)90180-3. [DOI] [PubMed] [Google Scholar]
  15. Li C., Chalfie M. Organogenesis in C. elegans: positioning of neurons and muscles in the egg-laying system. Neuron. 1990 May;4(5):681–695. doi: 10.1016/0896-6273(90)90195-l. [DOI] [PubMed] [Google Scholar]
  16. Mongan N. P., Baylis H. A., Adcock C., Smith G. R., Sansom M. S., Sattelle D. B. An extensive and diverse gene family of nicotinic acetylcholine receptor alpha subunits in Caenorhabditis elegans. Receptors Channels. 1998;6(3):213–228. [PubMed] [Google Scholar]
  17. Okkema P. G., Harrison S. W., Plunger V., Aryana A., Fire A. Sequence requirements for myosin gene expression and regulation in Caenorhabditis elegans. Genetics. 1993 Oct;135(2):385–404. doi: 10.1093/genetics/135.2.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Raizen D. M., Lee R. Y., Avery L. Interacting genes required for pharyngeal excitation by motor neuron MC in Caenorhabditis elegans. Genetics. 1995 Dec;141(4):1365–1382. doi: 10.1093/genetics/141.4.1365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schafer W. R., Sanchez B. M., Kenyon C. J. Genes affecting sensitivity to serotonin in Caenorhabditis elegans. Genetics. 1996 Jul;143(3):1219–1230. doi: 10.1093/genetics/143.3.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schinkmann K., Li C. Localization of FMRFamide-like peptides in Caenorhabditis elegans. J Comp Neurol. 1992 Feb 8;316(2):251–260. doi: 10.1002/cne.903160209. [DOI] [PubMed] [Google Scholar]
  21. Squire M. D., Tornøe C., Baylis H. A., Fleming J. T., Barnard E. A., Sattelle D. B. Molecular cloning and functional co-expression of a Caenorhabditis elegans nicotinic acetylcholine receptor subunit (acr-2). Receptors Channels. 1995;3(2):107–115. [PubMed] [Google Scholar]
  22. Sze J. Y., Victor M., Loer C., Shi Y., Ruvkun G. Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant. Nature. 2000 Feb 3;403(6769):560–564. doi: 10.1038/35000609. [DOI] [PubMed] [Google Scholar]
  23. Treinin M., Chalfie M. A mutated acetylcholine receptor subunit causes neuronal degeneration in C. elegans. Neuron. 1995 Apr;14(4):871–877. doi: 10.1016/0896-6273(95)90231-7. [DOI] [PubMed] [Google Scholar]
  24. Trent C., Tsuing N., Horvitz H. R. Egg-laying defective mutants of the nematode Caenorhabditis elegans. Genetics. 1983 Aug;104(4):619–647. doi: 10.1093/genetics/104.4.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Waggoner L. E., Dickinson K. A., Poole D. S., Tabuse Y., Miwa J., Schafer W. R. Long-term nicotine adaptation in Caenorhabditis elegans involves PKC-dependent changes in nicotinic receptor abundance. J Neurosci. 2000 Dec 1;20(23):8802–8811. doi: 10.1523/JNEUROSCI.20-23-08802.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Waggoner L. E., Hardaker L. A., Golik S., Schafer W. R. Effect of a neuropeptide gene on behavioral states in Caenorhabditis elegans egg-laying. Genetics. 2000 Mar;154(3):1181–1192. doi: 10.1093/genetics/154.3.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Waggoner L. E., Zhou G. T., Schafer R. W., Schafer W. R. Control of alternative behavioral states by serotonin in Caenorhabditis elegans. Neuron. 1998 Jul;21(1):203–214. doi: 10.1016/s0896-6273(00)80527-9. [DOI] [PubMed] [Google Scholar]
  28. Weinshenker D., Garriga G., Thomas J. H. Genetic and pharmacological analysis of neurotransmitters controlling egg laying in C. elegans. J Neurosci. 1995 Oct;15(10):6975–6985. doi: 10.1523/JNEUROSCI.15-10-06975.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Williams B. D. Genetic mapping with polymorphic sequence-tagged sites. Methods Cell Biol. 1995;48:81–96. doi: 10.1016/s0091-679x(08)61384-9. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES