Evolutionary Relationship of the Ligand-Gated Ion Channels and the Avermectin-Sensitive,Glutamate-Gated Chloride Channels |
| |
| Authors: | Demetrios K Vassilatis Keith O Elliston Philip S Paress Michel Hamelin Joseph P Arena James M Schaeffer Lex HT Van der Ploeg Doris F Cully |
| |
| Institution: | (1) Department of Genetics and Molecular Biology, RY80Y-305, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065-0900, USA, US;(2) Department of Genetics and Development, Columbia University, College of Physicians and Surgeons, 701 W. 168th Street, New York, NY 10032, USA, US;(3) Department of Bioinformatics, RY80Y-305, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065-0900, USA, US;(4) Department of Cell Biochemistry and Physiology, RY80Y-305, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065-0900, USA, US |
| |
| Abstract: | Two cDNAs, GluClα and GluClβ, 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 GluClα and GluClβ have pharmacological profiles distinct from the glutamate-gated cation channels as
well as the γ-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 GluClα and GluClβ 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 GluClα and GluClβ 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 GluClα and GluClβ, 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 GluClα and GluClβ belong to a discrete ligand-gated ion channel
family that may represent genes orthologous to the vertebrate glycine channels.
Received: 30 September 1996 / Accepted: 15 November 1996 |
| |
| Keywords: | : Avermectin — Phylogenetics — Caenorhabditis elegans— Glutamate |
| 本文献已被 SpringerLink 等数据库收录！ |
|
