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| Journal Article | FZJ-2026-02583 |
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2026
Wiley-VCH
Weinheim
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Please use a persistent id in citations: doi:10.1002/advs.202515481
Abstract: γ-aminobutyric acid (GABA) is the predominant inhibitory transmitter in the vertebrate nervous system. Fast inhibitory signaling is mediated by type A GABA receptors (GABAARs). While GABA is also present in plants and prokaryotes, it is unknown when it was first used for fast neuronal transmission. Cnidaria represent a sister group to all Bilateria and possess a variety of putative GABAARs, none of which has been functionally characterized. In this study, we surveyed putative inhibitory ion channel receptors from four different cnidarians. Phylogenetic analysis reveals a surprising phylogenetic complexity of these receptors. While the majority form a cnidarian-specific radiation, others cluster with bilaterian receptors. We functionally analyze seven putative Nematostella GABAARs of the cnidarian radiation and find that none is activated by GABA or glycine, whereas three are activated by glutamate. Using site-directed mutagenesis, we identify a lysine residue in the canonical ligand-binding pocket that is important for activation by glutamate. Our results identify a group of inhibitory ion channel receptors in Cnidaria that use glutamate as a ligand. Moreover, they suggest that inhibitory ion channel receptors in Cnidaria massively diversified, which may have been instrumental in the evolution of complex behaviors and sensory processing by the cnidarian nervous system.
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