Evolution of glutamatergic signaling and synapses

NEUROPHARMACOLOGY

卷:199

Review

Moroz, Leonid L.^1,2,3  Nikitin, Mikhail A.^4,5  Policar, Pavlin G.^1,6  Kohn, Andrea B.¹  Romanova, Daria Y.⁷ 

[1] Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL 32080 USA

[2] Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA

[3] Univ Florida, McKnight Brain Inst, Gainesville, FL 32610 USA

[4] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119991, Russia

[5] Russian Acad Sci, Kharkevich Inst Informat Transmission Problems, Moscow 127994, Russia

[6] Univ Ljubljana, Fac Comp & Informat Sci, SI-1000 Ljubljana, Slovenia

[7] Inst Higher Nervous Act & Neurophysiol, Cellular Neurobiol Learning Lab, Moscow 117485, Russia

关键词: Nervous system evolution;    Neurotransmitters;    Synapse;    Stress;    Aplysia;    Trichoplax;    Placozoa;    Ctenophores;    Eukaryotes;    Algae;    Glutamate receptors;    Vesicular glutamate transporters;    scRNA-seq;    Aspartate;    Glutamine;    GABA;    Cnidaria;   

DOI  :  10.1016/j.neuropharm.2021.108740

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free