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Glycine activated ion channel subunits encoded by ctenophore glutamate receptor genes

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [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
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.
Research Organization:
National Inst. of Health (NIH), Bethesda, MD (United States)
Sponsoring Organization:
National Aeronautics and Space Administration (NASA) (United States); National Inst. of Health (NIH) (United States); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Contributing Organization:
Univ. of Florida, St. Augustine, FL (United States)
Grant/Contract Number:
W-31109-ENG-38
OSTI ID:
1228098
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 44 Vol. 112; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Neto-α Controls Synapse Organization and Homeostasis at the Drosophila Neuromuscular Junction journal July 2020
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Structural mechanisms of activation and desensitization in neurotransmitter-gated ion channels journal June 2016
Chemosensory adaptations of the mountain fly Drosophila nigrosparsa (Insecta: Diptera) through genomics’ and structural biology’s lenses journal March 2017
The structural bases for agonist diversity in an Arabidopsis thaliana glutamate receptor-like channel journal December 2019
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Neto-α controls synapse organization and homeostasis at the Drosophila neuromuscular junction posted_content October 2019
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