Journal of Molecular Evolution

, Volume 69, Issue 2, pp 125–141 | Cite as

Aplysia cys-loop Glutamate-Gated Chloride Channels Reveal Convergent Evolution of Ligand Specificity

  • JacSue Kehoe
  • Svetlana Buldakova
  • Francine Acher
  • Joseph Dent
  • Piotr Bregestovski
  • Jonathan Bradley


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.


Aplysia Glutamate Glycine LGICs Chloride channels Phylogeny Glycine binding pocket motif 



JacSue Kehoe would like to thank Cristina Alberini for her invaluable instruction at the beginning of the cloning of the two subunits; Philippe Djian, Eric Krejci, and Bruno della Gaspera for generously making their equipment available to her; Russell English for his help with preparation of the figures; Jean Deutsch and David Enard for their help and patience while introducing her to some of the basics of phylogenetic analysis, and Robert Zucker of Cell and Molecular Biology at U.C. Berkeley for welcoming her as a Visiting Scholar. A last but not least word of thanks to the DOE Joint Genome Institute for making their work in progress available to the scientific community. This work was supported in part by the NEUROCYPRES grant from the European Commission Seventh Framework Programme (for S.B.).

Supplementary material

239_2009_9256_MOESM1_ESM.pdf (559 kb)
Supplementary material 1 (PDF 559 kb)


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • JacSue Kehoe
    • 1
    • 2
  • Svetlana Buldakova
    • 3
  • Francine Acher
    • 4
  • Joseph Dent
    • 5
  • Piotr Bregestovski
    • 3
  • Jonathan Bradley
    • 1
  1. 1.Laboratoire de Physiologie Cérébrale, CNRS, UMR 8118Université Paris DescartesParisFrance
  2. 2.Department of Molecular and Cell BiologyUniversity of CaliforniaBerkeleyUSA
  3. 3.INMED/INSERM U901 Institut de Neurobiologie de la MéditerranéeMarseilleFrance
  4. 4.Départment de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS, UMR 8601Université Paris DescartesParisFrance
  5. 5.Department of BiologyMcGill UniversityMontrealCanada

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