GLUD2 MaxPab Antibody
- Known as:
- GLUD2 MaxPab Antibody
- Catalog number:
- BIN-002747-B02
- Product Quantity:
- 0.05ml
- Category:
- -
- Supplier:
- Zyagen
- Gene target:
- GLUD2 MaxPab Antibody
Related genes to: GLUD2 MaxPab 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 MaxPab Antibody
Related articles to: GLUD2 MaxPab Antibody
- The GluD1 receptor has many unusual features including expression at both excitatory and inhibitory synapses and a ligand binding domain capable of binding both D-serine and GABA. We have previously demonstrated that striatal GluD1 is critical for the regulation of behavioral flexibility, a phenotype dependent on the cholinergic system. Here, we found that GluD1 is enriched postsynaptically at cholinergic synapses in the mouse and monkey dorsal striatum. Further, loss of GluD1 reduces the abundance of cholinergic terminals, excitatory responses at cholinergic synapses as well as muscarinic receptor-induced plasticity. In addition, optogenetic stimulation of cholinergic interneurons or puff-application of ACh, in the presence of cholinergic and AMPA/GABA receptor blockers, produced current responses in medium spiny neurons (MSNs) that were sensitive to the GluD1-channel blocker NASPM. These responses were absent in GluD1 KO and overexpression of GluD1 on KO background rescued Ach puff-induced currents suggesting potential conductance via GluD1. Finally, using GluD1-Cbln1 interaction assay as an indirect method to evaluate ligand binding interaction, we found that ACh can bind GluD1 and induce conformational changes. A similar ACh-induced conformational change was observed for GluD2 in the cell binding assay. Importantly, molecular dynamics simulations and mutagenesis analysis demonstrated that ACh binding orientation in the GluD1 ligand binding domain is different from D-serine and GABA. Overall, our results identified an unprecedented feature of GluD1 in the regulation of cholinergic synapses. - Source: PubMed
Publication date: 2026/06/10
Chettiar Poojashree BS Narasimhan Kishore KumarSabnis Siddhesh SEricksen Spencer SChoi DianeSmith YolandDravid Shashank M - 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