title: Caenorhabditis elegans nicotinic acetylcholine receptors are required for nociception.
abstract: Polymodal nociceptors sense and integrate information on injurious mechanical, thermal, and chemical stimuli. Chemical signals either activate nociceptors or modulate their responses to other stimuli. One chemical known to activate or modulate responses of nociceptors is acetylcholine (ACh). Across evolution nociceptors express subunits of the nicotinic acetylcholine receptor (nAChR) family, a family of ACh-gated ion channels. The roles of ACh and nAChRs in nociceptor function are, however, poorly understood. Caenorhabditis elegans polymodal nociceptors, PVD, express nAChR subunits on their sensory arbor. Here we show that mutations reducing ACh synthesis and mutations in nAChR subunits lead to defects in PVD function and morphology. A likely cause for these defects is a reduction in cytosolic calcium measured in ACh and nAChR mutants. Indeed, overexpression of a calcium pump in PVD mimics defects in PVD function and morphology found in nAChR mutants. Our results demonstrate, for the first time, a central role for nAChRs and ACh in nociceptor function and suggest that calcium permeating via nAChRs facilitates activity of several signaling pathways within this neuron.
authors: Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Hebrew University - Hadassah Medical School, Jerusalem 91120, Israel.
authors: Emiliano
authors: E
authors: Cohen
authors: Cell Biology Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge UK.
authors: Marios
authors: M
authors: Chatzigeorgiou
authors: Functional Genomics and Proteomics, KU Leuven, Naamsestraat 59, B-3000 Leuven, Belgium; SPHERE - Systemic Physiological & Ecotoxicological Research, Department of Biology, University of Antwerp, Groenenborgerlaan 171/U7, B-2020 Antwerp, Belgium.
authors: Steven J
authors: SJ
authors: Husson
authors: Buchmann Institute for Molecular Life Sciences and Institute of Biochemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 15, D-60438 Frankfurt, Germany.
authors: Wagner
authors: W
authors: Steuer-Costa
authors: Buchmann Institute for Molecular Life Sciences and Institute of Biochemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 15, D-60438 Frankfurt, Germany.
authors: Alexander
authors: A
authors: Gottschalk
authors: Cell Biology Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge UK.
authors: William R
authors: WR
authors: Schafer
authors: Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Hebrew University - Hadassah Medical School, Jerusalem 91120, Israel. Electronic address: millet_t@cc.huji.ac.il.
authors: Millet
authors: M
authors: Treinin
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D059225:Nociception; D009619:Nociceptors / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C454142:DEG-3 protein, C elegans; D011978:Receptors, Nicotinic; D000109:Acetylcholine
keywords: Acetylcholine; Caenorhabditis elegans; Calcium; Nicotinic acetylcholine receptors; Polymodal nociceptors