ReviewNeuropharmacology2021
Evolution of glutamatergic signaling and synapses.
Review in Neuropharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 76 citations in OpenAlex.
- Neurotransmitter receptor-associated gene signature: prognostic and immunosuppressive microenvironment in NSCLC.Future science OA · 2026Article
- Tunable AMPA receptor function via recurrent evolution of heterotetramers.The Journal of general physiology · 2026Article
- Functional Analysis of Ligand-Gated Chloride Channels in a Cnidarian Sheds Light on the Evolution of Inhibitory Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanism of Ammonia-Induced Brain Damage in Chinese Striped-Necked Turtle (Mauremys sinensis).Integrative zoology · 2026Article
- HS-AssociatedMicroorganisms · 2025Article
- Spatiotemporal Patterns of Gene Expression Associated With Mating Stimuli in the Brain of Female Guppies.Genes, brain, and behavior · 2025Article
- Elucidating the material basis and therapeutic mechanisms of Shaoma Zhijing granules for tourette syndrome by UPLC/Q-TOF-MS and multiple models.Metabolic brain disease · 2025Article
- Multilayer control of KaiR1D-autoreceptor function by the auxiliary protein Neto.bioRxiv : the preprint server for biology · 2025Article
- Essence of Chicken Supplementation Alters Brain and Blood Metabolite Signatures in Sleep-Deprived Mice.Metabolites · 2025Article
- Evolution of iGluR ligand specificity, polyamine regulation, and ion selectivity inferred from a placozoan epsilon receptor.Communications biology · 2025Article
- Vitamin C Modulates the PI3K/AKT Pathway via Glutamate and Nitric Oxide in Developing Avian Retina Cells in Culture.Brain sciences · 2025Article
- Depletion of HSP60 in Microglia Leads to Synaptic Dysfunction and Depression-Like Behaviors Through Enhanced Synaptic Pruning in Male Mice.CNS neuroscience & therapeutics · 2025Article
- Intranasal Delivery of Lithium Salt Suppresses Inflammatory Pyroptosis in the Brain and Ameliorates Memory Loss and Depression-like Behavior in 5XFAD Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- ATP and glutamate coordinate contractions in the freshwater sponge Ephydatia muelleri.The Journal of experimental biology · 2025Article
- The analgesic mechanism of electroacupuncture at the central level for neuropathic pain: a review of studies based on animal experiments.Frontiers in neurology · 2025Review
- Intranasal Delivery of Lithium Salt Suppresses Inflammatory Pyroptosis in the brain and Ameliorates Memory Loss and Depression-like Behavior in 5XFAD mice.bioRxiv : the preprint server for biology · 2024Article
- Making Neurobots and Chimerical Ctenophores.bioRxiv : the preprint server for biology · 2024Article
- Glutamate and excitotoxicity in central nervous system disorders: ionotropic glutamate receptors as a target for neuroprotection.Neuroprotection (Chichester, England) · 2024Review
- Channels of Evolution: Unveiling Evolutionary Patterns in Diatom CaPlants (Basel, Switzerland) · 2024Article
- Recording Cilia Activity in Ctenophores.Methods in molecular biology (Clifton, N.J.) · 2024Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
Glutamate (Glu) is the primary excitatory transmitter in the mammalian brain. But, we know little about the evolutionary history of this adaptation, including the selection of l-glutamate as a signaling molecule in the first place. Here, we used comparative metabolomics and genomic data to reconstruct the genealogy of glutamatergic signaling. The origin of Glu-mediated communications might be traced to primordial nitrogen and carbon metabolic pathways. The versatile chemistry of L-Glu placed this molecule at the crossroad of cellular biochemistry as one of the most abundant metabolites. From there, innovations multiplied. Many stress factors or injuries could increase extracellular glutamate concentration, which led to the development of modular molecular systems for its rapid sensing in bacteria and archaea. More than 20 evolutionarily distinct families of ionotropic glutamate receptors (iGluRs) have been identified in eukaryotes. The domain compositions of iGluRs correlate with the origins of multicellularity in eukaryotes. Although L-Glu was recruited as a neuro-muscular transmitter in the early-branching metazoans, it was predominantly a non-neuronal messenger, with a possibility that glutamatergic synapses evolved more than once. Furthermore, the molecular secretory complexity of glutamatergic synapses in invertebrates (e.g., Aplysia) can exceed their vertebrate counterparts. Comparative genomics also revealed 15+ subfamilies of iGluRs across Metazoa. However, most of this ancestral diversity had been lost in the vertebrate lineage, preserving AMPA, Kainate, Delta, and NMDA receptors. The widespread expansion of glutamate synapses in the cortical areas might be associated with the enhanced metabolic demands of the complex brain and compartmentalization of Glu signaling within modular neuronal ensembles.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.