通过结合生化、结构和功能分析，研究人员证明了GluD1结合GABA，这是嗜离子性谷氨酸受体（iGluR）中前所未有的特征。GluD1激活通过依赖于跨突触锚定的非嗜离子性机制，在成年小鼠海马中产生持久的GABA能突触电流增强。GluD1作为GABA受体控制抑制性突触可塑性的发现挑战了经典的谷氨酸能受体和GABA能受体之间的对立。
据了解，脊椎动物中枢神经系统的快速突触神经传递主要依赖于驱动神经元兴奋的iGluR和负责神经元抑制的A型γ-氨基丁酸受体（GABAAR）。然而，GluD1受体，一种iGluR家族成员，同时存在于兴奋性和抑制性突触。GluD1激活是否以及如何影响抑制性神经传递尚不清楚。
附：英文原文
Title: GluD1 binds GABA and controls inhibitory plasticity
Author: Laura Piot, Christina Heroven, Simon Bossi, Joseph Zamith, Tomas Malinauskas, Chris Johnson, Doris Wennagel, David Stroebel, Cécile Charrier, A. Radu Aricescu, Laetitia Mony, Pierre Paoletti
Issue&Volume: 2023-12-07
Abstract: Fast synaptic neurotransmission in the vertebrate central nervous system relies primarily on ionotropic glutamate receptors (iGluRs), that drive neuronal excitation, and type A γ-aminobutyric acid receptors (GABAARs), 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 impact inhibitory neurotransmission is unknown. Here, using a combination of biochemical, structural and functional analyses, we demonstrate that GluD1 binds GABA, an unprecedented feature for iGluRs. GluD1 activation produces long-lasting enhancement of GABAergic synaptic currents in the adult mouse hippocampus through a non-ionotropic mechanism 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.
DOI: adf3406
Source: https://www.science.org/doi/10.1126/science.adf3406