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Title: Glycine activated ion channel subunits encoded by ctenophore glutamate receptor genes

Recent genome projects for ctenophores have revealed the presence of numerous ionotropic glutamate receptors (iGluRs) in Mnemiopsis leidyi and Pleurobrachia bachei, among our earliest metazoan ancestors. Sequence alignments and phylogenetic analysis show that these form a distinct clade from the well-characterized AMPA, kainate, and NMDA iGluR subtypes found in vertebrates. Although annotated as glutamate and kainate receptors, crystal structures of the ML032222a and PbiGluR3 ligand-binding domains (LBDs) reveal endogenous glycine in the binding pocket, whereas ligand-binding assays show that glycine binds with nanomolar affinity; biochemical assays and structural analysis establish that glutamate is occluded from the binding cavity. Further analysis reveals ctenophore-specific features, such as an interdomain Arg-Glu salt bridge, present only in subunits that bind glycine, but also a conserved disulfide in loop 1 of the LBD that is found in all vertebrate NMDA but not AMPA or kainate receptors. In this paper, we hypothesize that ctenophore iGluRs are related to an early ancestor of NMDA receptors, suggesting a common evolutionary path for ctenophores and bilaterian species, and finally suggest that future work should consider both glycine and glutamate as candidate neurotransmitters in ctenophore species.
 [1] ;  [1] ;  [1] ;  [2] ;  [1]
  1. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Child Health and Human Development. Lab. of Cellular and Molecular Neurophysiology
  2. Univ. of Florida, St. Augustine, FL (United States). The Whitney Lab. for Marine Bioscience
Publication Date:
Grant/Contract Number:
W-31-109-Eng-38; 00093371
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 112; Journal Issue: 44; Journal ID: ISSN 0027-8424
National Academy of Sciences, Washington, DC (United States)
Research Org:
National Inst. of Health (NIH), Bethesda, MD (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Inst. of Health (NIH) (United States); National Aeronautic and Space Administration (NASA)
Contributing Orgs:
Univ. of Florida, St. Augustine, FL (United States)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; NMDA receptors; ctenophores; crystal structures; evolution
OSTI Identifier: