Originally published In Press as doi:10.1074/jbc.M404370200 on August 2, 2004
Originally published In Press as doi:10.1074/jbc.M404370200 on July 27, 2004
J. Biol. Chem., Vol. 279, Issue 41, 42476-42483, October 8, 2004
The Caenorhabditis elegans unc-63 Gene Encodes a Levamisole-sensitive Nicotinic Acetylcholine Receptor 
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||||
From the
Medical Research Council Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, United Kingdom, ||Department of Zoology and The Babraham Institute Laboratory of Molecular Signalling, University of Cambridge, Downing Street, Cambridge CB2 3EJ, United Kingdom, and **Department of Biology, University of Illinois, Chicago, Illinois 60607
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 12 genes, three 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-resistant gene, unc-63, encoding a nAChR 
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 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 types (UNC-38 and UNC-63) and two non- types (UNC-29 and LEV-1), can contribute to levamisole-sensitive muscle nAChRs in nematodes.
Received for publication, April 20, 2004
, and in revised form, July 23, 2004.
* This work was supported by grants from the Medical Research Council (to E. C., H. A. B., and D. B. S.) and the Biotechnology and Biosciences Research Council (to E. C. and D. B. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AAK83056/I>
¶ Present address: Laboratoire de Génétique Moléculaire, Institut de Génétique et Microbiologie, Unité Mixte de Recherche 8621, Université Paris XI, B
t. 400, 91405 Orsay Cedex, France.
Present address: Dept. of Pediatric Haematology and Oncology, Massachusetts General Hospital, Boston, MA 02114.
Present address: Dept. of Clinical Veterinary Medicine, University of Cambridge, Cambridge CB3 OES, UK.
¶¶ Present address: Occupational and Safety Programs, University of Texas, San Antonio, TX 78249.
|||| To whom correspondence should be addressed. Tel.: 44-1865-272-145; Fax: 44-1865-282-651; E-mail: david.sattelle{at}anat.ox.ac.uk.
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Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.
