GluD1 binds GABA and controls inhibitory plasticity

• 成果类型: Article
• 署名作者: Piot, Laura; Heroven, Christina; Bossi, Simon; Zamith, Joseph; Malinauskas, Tomas; Johnson, Chris; Wennagel, Doris; Stroebel, David; Charrier, Cecile; Aricescu, A. Radu; Mony, Laetitia; Paoletti, Pierre
• 署名单位: Institut National de la Sante et de la Recherche Medicale (Inserm); Universite PSL; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); MRC Laboratory Molecular Biology; University of Oxford; Wellcome Centre for Human Genetics; Chinese Academy of Medical Sciences - Peking Union Medical College; University of Oxford
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9224
• DOI: 10.1126/science.adf3406
• 发表日期: 2023-12-22
• 页码: 1389-1394
• 关键词: synapse formation; ligand-binding; d-serine; presynaptic differentiation; receptor delta-2; glutamate; channel; domain; pharmacology; proteins

摘要

Fast synaptic neurotransmission in the vertebrate central nervous system relies primarily on ionotropic glutamate receptors (iGluRs), which drive neuronal excitation, and type A gamma-aminobutyric acid receptors (GABAARs), which are responsible for neuronal inhibition. However, the GluD1 receptor, an iGluR family member, is present at both excitatory and inhibitory synapses. Whether and how GluD1 activation may affect inhibitory neurotransmission is unknown. In this work, by using a combination of biochemical, structural, and functional analyses, we demonstrate that GluD1 binds GABA, a previously unknown feature of iGluRs. GluD1 activation produces long-lasting enhancement of GABAergic synaptic currents in the adult mouse hippocampus through a non-ionotropic mechanism that is dependent on trans-synaptic anchoring. The identification of GluD1 as a GABA receptor that controls inhibitory synaptic plasticity challenges the classical dichotomy between glutamatergic and GABAergic receptors.