acr-16 Encodes an Essential Subunit of the Levamisole-resistant Nicotinic Receptor at the Caenorhabditis elegans Neuromuscular Junction
Year: 2005
Type: article
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.
Source: Journal of Biological Chemistry
Institutions: University of Illinois Chicago, Vanderbilt University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funders: Vanderbilt University, National Institutes of Health, National Heart, Lung, and Blood Institute, National Eye Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: MOLECULAR PHYSIOLOGY OF MEMBRANE TRANSPORT IN C ELEGANS, Eunice Kennedy Shriver Intellectual and Developmental Disability Research Center, G1461957898, G150953014, G153582612, G1931562587, G290735076, G291339886, VANDERBILT NIDDK BIOTECHNOLOGY CENTER, G3433274139, G3865556588, UNC-18 function in C. elegans synaptic transmission, G4320917349, G43430121, G4671382230, Molecular Genetics of Neural Specificity, G5357041942, G5394510305, G577112812, G5853943267, G695801743, G7220527126, G8391480415, Diabetes Research and Training Center, G9000060478, G9000081609, G9000083539, G9000106052, G9000127534, G9000135199, G9000159340, G9000222329, Molecular and Cellular Basis for Digestive Diseases
OpenAlex ID: W1971083012