Ask about this productRelated genes to: GLUD2 antibody
- Gene:
- GLUD2 NIH gene
- Name:
- glutamate dehydrogenase 2
- Previous symbol:
- GLUDP1
- Synonyms:
- -
- Chromosome:
- Xq24
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2016-10-05
Related products to: GLUD2 antibody
Related articles to: GLUD2 antibody
- The delta-type ionotropic glutamate receptors (iGluRs) GluD1 and GluD2 are ligand-gated ion channels that are fundamental for regulating both excitatory and inhibitory synapses. Rising evidence points to the role of GluD1 in the development of neurological diseases. However, the ultrastructure of human GluD1 (hGluD1) and the molecular basis for its ligand-gating remain unclear. Here, we define the structure of hGluD1 and resolve its ligand-gating mechanism using cryo-electron microscopy (cryoEM) and single channel bilayer recording. While hGluD1 exhibits a non-swapped architecture, it contains conserved iGluR moieties that enable ligand-gating, such as a ligand-binding domain (LBD) tethered to a transmembrane ion channel. Binding of the neurotransmitter γ-aminobutyric acid (GABA) or D-serine to the LBD enables cation influx through the hGluD1 ion channel. Our findings delineate the molecular architecture and function of hGluD1, provide foundations for understanding patient mutations in hGluD1, and will invigorate therapeutic development against hGluD1. - Source: PubMed
Publication date: 2026/04/08
Mondal Anish KumarWang HaoboWeaver Mae GZheng IrisKormshchikov NikitaAhmed FairineTwomey Edward C - For decades, delta glutamate receptors were considered ‘orphan’ receptors: they resembled ion channels structurally but appeared functionally silent in standard room-temperature electrophysiological assays. Recent studies have shown that their activation is governed by a high energetic barrier, a distinctive structural asymmetry and a strong dependence on physiological temperature (37 °C). This thermodynamic gating mechanism, along with recent evolutionary insights, is redefining their role from passive scaffolds to dynamic participants in synaptic physiology. - Source: PubMed
Publication date: 2026/02/25
Vinnakota RajeshKumar Janesh - Spinocerebellar ataxia type 14 (SCA14) is an autosomal-dominant disorder caused by more than 80 PRKCG missense variants encoding protein kinase Cγ (PKCγ), a serine/threonine kinase highly enriched in Purkinje cells (PCs). Despite typically late onset and slow progression, the molecular basis of age-related decline remains unclear. We used a somatic in vivo approach to express wild-type (WT) PKCγ-GFP or the prototypical G128D PKCγ-GFP selectively in PCs of neonatal mice via an adeno-associated virus (AAV) under a PC-specific promoter. G128D PKCγ-GFP formed cytoplasmic aggregates, mislocalized PCs during development, and produced gait deficits by 4 weeks that worsened with age, despite preserved PC counts and overall cerebellar volume at 1.5 years. Immunohistochemistry revealed a selective vulnerability of climbing-fiber (CF) input: vesicular glutamate transporter 2 (VGLUT2), a marker of CF synapses, declined significantly from 12 to 60 weeks in G128D mice, and the VGLUT2-positive innervation field was narrower than age-matched WT at both time points. By contrast, the glutamate/aspartate transporter GLAST in Bergmann-glial radial processes was reduced predominantly at 12 weeks in G128D mice. The δ2 glutamate receptor (GluD2) at parallel fibers and glial fibrillary acidic protein (GFAP) decreased with age but were comparable between expression conditions. Notably, aggregated mutant PKCγ accumulated within the axon initial segment (AIS), whose architecture progressively deteriorated; the altered AIS excluded PKCγ-GFP from distal axons and, by 60 weeks, was associated with reduced delivery of the vesicular GABA transporter (VGAT) to deep cerebellar nuclei (DCN), consistent with impaired anterograde transport. Hence, rather than overt neuronal loss, the cumulative burden of G128D-specific CF/axonal deficits and age-accentuated circuit and glial changes-reduced GLAST function and decreased GluD2-accounts for the worsening motor phenotype. This AAV-based system provides a practical platform to dissect late-onset pathogenic mechanisms and evaluate therapeutic strategies in vivo. - Source: PubMed
Adachi NaokoKoganemaru IzumiWanying FengMatsushita NaoyaNakayama TomoyoshiSeki TakahiroKonno AyumuHirai HirokazuSaito NaoakiUeyama Takehiko - Delta-type ionotropic glutamate receptors (iGluRs, also known as GluDs) are members of the iGluR ligand-gated ion channel family, yet their function remains unknown. Although GluDs are widely expressed in the brain, have key roles in synaptic organization, and harbour disease-linked mutations, whether they retain iGluR-like channel function is debated as currents have not been directly observed. Here we define GluDs as ligand-gated ion channels that are tightly regulated in cellular contexts by purifying human GluD2 (hGluD2) and directly characterizing its structure and function using cryo-electron microscopy and bilayer recordings. We show that hGluD2 is activated by D-serine and GABA (γ-aminobutyric acid), with augmented activation at physiological temperatures. We reveal that hGluD2 contains an ion channel directly coupled to clamshell-like ligand-binding domains, which are coordinated by the amino-terminal domain above the ion channel. Ligand binding triggers channel opening via an asymmetric mechanism, and a cerebellar ataxia point mutation in the ligand-binding domain rearranges the receptor architecture and induces leak currents. Our findings demonstrate that GluDs possess the intrinsic biophysical properties of ligand-gated ion channels, reconciling prior conflicting observations to establish a framework for understanding their cellular regulation and for developing therapies targeting GluD2. - Source: PubMed
Publication date: 2025/09/16
Wang HaoboAhmed FairineKhau JeffreyMondal Anish KumarTwomey Edward C - The plasticity of ionotropic receptors (mainly AMPARs and NMDARs) within the glutamatergic system has long been investigated as a mechanism for physiological and pathological adaptive learning. The tetrameric delta glutamate receptors (δGluRs, GluD1 and GluD2) are also classified as ionotropic glutamate receptors, however they are insensitive to glutamate. These proteins, especially GluD1, have been implicated in multiple psychiatric conditions and play a functional role in synapses assembly and stability, but recent evidence suggests that they also may supply a tonic excitatory conductance, are sensitive to poly-amine blockade, and regulate synaptic plasticity. GluD1 expression has been noted in the dorsolateral bed nucleus of the stria terminalis (dlBNST), but its function in this region remains unknown. - Source: PubMed
Publication date: 2025/08/18
Conley Sara YSizer Sarah EBedard Madigan LFaccidomo SaraHodge Clyde WMcElligott Zoé A