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A more recent version of this article appeared on October 8, 2004 Originally published In Press as doi:10.1074/jbc.M404370200 on August 2, 2004
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Papers In Press, published online ahead of print July 27, 2004
J. Biol. Chem, 10.1074/jbc.M404370200
Submitted on April 20, 2004
Revised on July 23, 2004
Accepted on July 27, 2004

The caenorhabditis elegans unc-63 gene encodes a levamisole-sensitive nicotinic acetylcholine receptor alpha subunit

Emmanuel Culetto, Howard A. Baylis, Janet E. Richmond, Andrew K. Jones, John T. Fleming, Michael D. Squire, James A. Lewis, and David B. Sattelle

Human Anatomy and Genetics, University of Oxford, Oxford OX1 3QX

Corresponding Author: david.sattelle{at}anat.ox.ac.uk

The anthelmintic drug, levamisole, causes hypercontraction of body-wall muscles and lethality in nematode worms. In the nematode Caenorhabditis elegans, a genetic screen for levamisole resistance has identified 11 genes, 3 of which (unc-38, unc-29 and lev-1) encode nicotinic acetylcholine receptor (nAChR) subunits. Here we describe the molecular and functional characterization of another levamisole-resistance gene, unc-63, encoding a nAChR alpha subunit with a predicted amino acid sequence most similar to that of UNC-38. Like UNC-38 and UNC-29, UNC-63 is expressed in body wall muscles. In addition, UNC-63 is expressed in vulval muscles and neurons. We also show that the LEV-1 is expressed in body wall muscle, thus overlapping the cellular localization of UNC-63, UNC-38 and UNC-29 and suggesting possible association in vivo. This is supported by electrophysiological studies on body wall muscle, which demonstrate that a levamisole-sensitive nAChR present at the C. elegans neuromuscular junction requires both UNC-63 and LEV-1 subunits. Thus, at least four subunits, two alpha types (UNC-38 and UNC-63) and two non-alpha types (UNC-29 and LEV-1), can contribute to levamisole-sensitive muscle nAChRs in nematodes.


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