Caenorhabditis elegans levamisole resistance genes lev-1, unc-29, and unc-38 encode functional nicotinic acetylcholine receptor subunits

John T. Fleming, Michael D. Squire, Thomas M. Barnes, Camilla Tornoe, Kazuhiko Matsuda, Joohong Ahnn, Andrew Fire, John E. Sulston, Eric A. Barnard, David B. Sattelle, James A. Lewis

    Research output: Contribution to journalArticlepeer-review

    Abstract

    We show that three of the eleven genes of the nematode Caenorhabditis elegans that mediate resistance to the nematocide levamisole and to other cholinergic agonists encode nicotinic acetylcholine receptor (nAChR) subunits. unc-38 encodes an α subunit while lev-1 and unc-29 encode non-α subunits. The nematode nAChR subunits show conservation of many mammalian nAChR sequence features, implying an ancient evolutionary origin of nAChR proteins. Expression in Xenopus oocytes of combinations of these subunits that include the unc-38 α subunit results in levamisole-induced currents that are suppressed by the nAChR antagonists mecamylamine, neosurugatoxin, and d-tubocurarine but not α-bungarotoxin. The mutant phenotypes reveal that unc-38 and unc-29 subunits are necessary for nAChR function, whereas the lev- 1 subunit is not. An UNC-29-GFP fusion shows that UNC-29 is expressed in body and head muscles. Two dominant mutations of lev-1 result in a single amino acid substitution or addition in or near transmembrane domain 2, a region important to ion channel conductance and desensitization. The identification of viable nAChR mutants in C. elegans provides an advantageous system in which receptor expression and synaptic targeting can be manipulated and studied in vivo.
    Original languageEnglish
    Pages (from-to)5843-5857
    Number of pages14
    JournalJournal of Neuroscience
    Volume17
    Issue number15
    Publication statusPublished - 1 Aug 1997

    Keywords

    • Acetylcholine receptor
    • Caenorhabditis elegans
    • Confocal microscopy
    • Evolution
    • GFP
    • lev- 1
    • Levamisole resistance genes
    • Nematode
    • Receptor localization
    • Receptor mutations
    • Transmembrane domain mutation
    • unc-29
    • Unc-38
    • Xenopus oocyte expression

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