Aplysia cys-loop glutamate-gated chloride channels reveal convergent evolution of ligand specificity.
Among the members of the superfamily of cys-loop ligand-gated ion channels (LGICs) are receptors distinguished by the presence of two cys-loops in the ligand-binding domain, for example, the glycine receptor. Such receptors have thus far been cloned only from vertebrates and from ecdysozoa (arthropods and nematodes). We have now cloned and expressed two 2-cys-loop receptors from Aplysia californica, a lophotrocozoan, and have shown that they form homomeric glutamate receptors. We have also built up a database including the two receptors cloned here, previously cloned vertebrate and ecdysozoan 2-cys-loop receptors taken from GenBank, and the same type of receptors obtained by a search of recently cloned genomes, including two non-vertebrate chordates, an echinoderm, a crustacean, an annelid, and another mollusk. We subjected these receptors to phylogenetic analysis, alone and in combination with GABA-A receptors from the same phyla and from a recently cloned cnidarian. The phylogenetic analysis revealed the presence of two independent clades of glutamate receptors: one from lophotrocozoa and other from ecdysozoa, and suggests that the ancestors of the current 2-cys-loop receptor types diverged from the GABA-A receptors and from each other before the bilateria-cnidaria split. Finally, combining the results from the phylogenetic analysis with those obtained from an analysis of the 2-cys-loop receptors in light of recently published hypotheses concerning the glycine binding pocket, we predict that glycine receptors are not exclusively a vertebrate-receptor type.
Kehoe
JacSue
J
CNRS, UMR, Université Paris Descartes, France. jacsue.kehoe@parisdescartes.fr
Buldakova
Svetlana
S
Acher
Francine
F
Dent
Joseph
J
Bregestovski
Piotr
P
Bradley
Jonathan
J
D000409:Alanine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000235:genetics*; D018118:Chloride Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism*; D019143:Evolution, Molecular; D005998:Glycine / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D007559:Ivermectin / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D010802:Phylogeny; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity / Q000187:drug effects
D018118:Chloride Channels; D008024:Ligands; D021122:Protein Subunits; D011963:Receptors, GABA-A; C109777:glutamate-gated chloride channels; D007559:Ivermectin; D003545:Cysteine; D000409:Alanine; D005998:Glycine