Caenorhabditis elegansLevamisole Resistance Geneslev-1,unc-29, andunc-38Encode Functional Nicotinic Acetylcholine Receptor Subunits

Open Access
Publisher Website
Google Scholar
Abstract
We show that three of the eleven genes of the nematodeCaenorhabditis elegansthat mediate resistance to the nematocide levamisole and to other cholinergic agonists encode nicotinic acetylcholine receptor (nAChR) subunits.unc-38encodes an α subunit whilelev-1andunc-29encode non-α subunits. The nematode nAChR subunits show conservation of many mammalian nAChR sequence features, implying an ancient evolutionary origin of nAChR proteins. Expression inXenopusoocytes of combinations of these subunits that include theunc-38α subunit results in levamisole-induced currents that are suppressed by the nAChR antagonists mecamylamine, neosurugatoxin, andd-tubocurarine but not α-bungarotoxin. The mutant phenotypes reveal thatunc-38andunc-29subunits are necessary for nAChR function, whereas thelev-1subunit is not. An UNC-29–GFP fusion shows that UNC-29 is expressed in body and head muscles. Two dominant mutations oflev-1result 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 inC. elegansprovides an advantageous system in which receptor expression and synaptic targeting can be manipulated and studiedin vivo.