TY - JOUR
T1 - The Caenorhabditis elegans unc-63 gene encodes a levamisole-sensitive nicotinic acetylcholine receptor α subunit
AU - Culetto, Emmanuel
AU - Baylis, Howard A.
AU - Richmond, Janet E.
AU - Jones, Andrew K.
AU - Fleming, John T.
AU - Squire, Michael D.
AU - Lewis, James A.
AU - Sattelle, David B.
N1 - R01 NS041477-01A1, NINDS NIH HHS, United StatesR01 NS041477-02, NINDS NIH HHS, United StatesR01 NS041477-03, NINDS NIH HHS, United States
PY - 2004/10/8
Y1 - 2004/10/8
N2 - 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 nAChE α 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 α types (UNC-38 and UNC-63) and two non-α types (UNC-29 and LEV-1), can contribute to levamisole-sensitive muscle nAChRs in nematodes.
AB - 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 nAChE α 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 α types (UNC-38 and UNC-63) and two non-α types (UNC-29 and LEV-1), can contribute to levamisole-sensitive muscle nAChRs in nematodes.
U2 - 10.1074/jbc.M404370200
DO - 10.1074/jbc.M404370200
M3 - Article
C2 - 15280391
SN - 1083-351X
VL - 279
SP - 42476
EP - 42483
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 41
ER -