Aplysia cys-loop glutamate-gated chloride channels reveal convergent evolution of ligand specificity

J Mol Evol. 2009 Aug;69(2):125-41. doi: 10.1007/s00239-009-9256-z. Epub 2009 Jun 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / pharmacology
  • Amino Acid Sequence
  • Animals
  • Aplysia / genetics*
  • Chloride Channels / chemistry
  • Chloride Channels / genetics
  • Chloride Channels / metabolism*
  • Cysteine / metabolism*
  • Evolution, Molecular*
  • Glycine / metabolism
  • Ion Channel Gating / drug effects
  • Ivermectin / metabolism
  • Ligands
  • Molecular Sequence Data
  • Phylogeny
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Receptors, GABA-A / metabolism
  • Sequence Alignment
  • Substrate Specificity / drug effects


  • Chloride Channels
  • Ligands
  • Protein Subunits
  • Receptors, GABA-A
  • glutamate-gated chloride channels
  • Ivermectin
  • Cysteine
  • Alanine
  • Glycine

Associated data

  • GENBANK/GQ148562
  • GENBANK/GQ148563