title: acr-16 encodes an essential subunit of the levamisole-resistant nicotinic receptor at the Caenorhabditis elegans neuromuscular junction.
abstract: The Caenorhabditis elegans neuromuscular junction (NMJ) contains three pharmacologically distinct ionotropic receptors: gamma-aminobutyric acid receptors, levamisole-sensitive nicotinic receptors, and levamisole-insensitive nicotinic receptors. The subunit compositions of the gamma-aminobutyric acid- and levamisole-sensitive receptors have been elucidated, but the levamisole-insensitive acetylcholine receptor is uncharacterized. To determine which of the approximately 40 putative nicotinic receptor subunit genes in the C. elegans genome encodes the levamisole-resistant receptor, we utilized MAPCeL, a microarray profiling strategy. Of seven nicotinic receptor subunit transcripts found to be enriched in muscle, five encode the levamisole receptor subunits, leaving two candidates for the levamisole-insensitive receptor: acr-8 and acr-16. Electrophysiological analysis of the acr-16 deletion mutant showed that the levamisole-insensitive muscle acetylcholine current was eliminated, whereas deletion of acr-8 had no effect. These data suggest that ACR-16, like its closest vertebrate homolog, the nicotinic receptor alpha7-subunit, may form homomeric receptors in vivo. Genetic ablation of both the levamisole-sensitive receptor and acr-16 abolished all cholinergic synaptic currents at the NMJ and severely impaired C. elegans locomotion. Therefore, ACR-16-containing receptors account for all non-levamisole-sensitive nicotinic synaptic signaling at the C. elegans NMJ. The determination of subunit composition for all three C. elegans body wall muscle ionotropic receptors provides a critical foundation for future research at this tractable model synapse.
authors.affiliation: Department of Biology, University of Illinois, Chicago, Illinois 60607, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Touroutine
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Fox
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Von Stetina
authors.forename: Anna
authors.initials: A
authors.lastname: Burdina
authors.forename: David M
authors.initials: DM
authors.lastname: Miller
authors.forename: Janet E
authors.initials: JE
authors.lastname: Richmond
mesh_terms: D000200:Action Potentials; D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry* / Q000166:cytology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D004351:Drug Resistance; D020869:Gene Expression Profiling; D007978:Levamisole / Q000494:pharmacology; D008124:Locomotion / Q000235:genetics; D009469:Neuromuscular Junction / Q000737:chemistry*; D021122:Protein Subunits; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000187:drug effects / Q000235:genetics*; D013569:Synapses
chemical_list: D029742:Caenorhabditis elegans Proteins; D021122:Protein Subunits; D011978:Receptors, Nicotinic; C099378:acr-16 protein, C elegans; D007978:Levamisole