title: Evolutionary relationship of the ligand-gated ion channels and the avermectin-sensitive, glutamate-gated chloride channels.
abstract: Two cDNAs, GluClalpha and GluClbeta, encoding glutamate-gated chloride channel subunits that represent targets of the avermectin class of antiparasitic compounds, have recently been cloned from Caenorhabditis elegans (Cully et al., Nature, 371, 707-711, 1994). Expression studies in Xenopus oocytes showed that GluClalpha and GluClbeta have pharmacological profiles distinct from the glutamate-gated cation channels as well as the gamma-aminobutyric acid (GABA)- and glycine-gated chloride channels. Establishing the evolutionary relationship of related proteins can clarify properties and lead to predictions about their structure and function. We have cloned and determined the nucleotide sequence of the GluClalpha and GluClbeta genes. In an attempt to understand the evolutionary relationship of these channels with the members of the ligand-gated ion channel superfamily, we have performed gene structure comparisons and phylogenetic analyses of their nucleotide and predicted amino acid sequences. Gene structure comparisons reveal the presence of several intron positions that are not found in the ligand-gated ion channel superfamily, outlining their distinct evolutionary position. Phylogenetic analyses indicate that GluClalpha and GluClbeta form a monophyletic subbranch in the ligand-gated ion channel superfamily and are related to vertebrate glycine channels/receptors. Glutamate-gated chloride channels, with electrophysiological properties similar to GluClalpha and GluClbeta, have been described in insects and crustaceans, suggesting that the glutamate-gated chloride channel family may be conserved in other invertebrate species. The gene structure and phylogenetic analyses in combination with the distinct pharmacological properties demonstrate that GluClalpha and GluClbeta belong to a discrete ligand-gated ion channel family that may represent genes orthologous to the vertebrate glycine channels.
authors.affiliation: Department of Genetics and Molecular Biology, RY80Y-305, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065-0900, USA. demetrios_vassilatis@merck.com
authors.forename: D K
authors.initials: DK
authors.lastname: Vassilatis
authors.forename: K O
authors.initials: KO
authors.lastname: Elliston
authors.forename: P S
authors.initials: PS
authors.lastname: Paress
authors.forename: M
authors.initials: M
authors.lastname: Hamelin
authors.forename: J P
authors.initials: JP
authors.lastname: Arena
authors.forename: J M
authors.initials: JM
authors.lastname: Schaeffer
authors.forename: L H
authors.initials: LH
authors.lastname: Van der Ploeg
authors.forename: D F
authors.initials: DF
authors.lastname: Cully
mesh_terms: D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000235:genetics*; D018118:Chloride Channels / Q000235:genetics*; D017238:Genes, Helminth / Q000235:genetics; D018698:Glutamic Acid / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007559:Ivermectin / Q000031:analogs & derivatives / Q000494:pharmacology; D008024:Ligands; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D000969:Antinematodal Agents; D018118:Chloride Channels; D008024:Ligands; D018698:Glutamic Acid; D007559:Ivermectin; C019264:avermectin