GLUD2 Blocking Peptide, Blocking Peptides
- Known as:
- GLUD2 Blocking Peptide, Blocking Peptides
- Catalog number:
- 33R-2428
- Product Quantity:
- 100 ug
- Category:
- -
- Supplier:
- Fitzgerald
- Gene target:
- GLUD2 Blocking Peptide Peptides
Related genes to: GLUD2 Blocking Peptide, Blocking Peptides
- 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 Blocking Peptide, Blocking Peptides
Related articles to: GLUD2 Blocking Peptide, Blocking Peptides
- Interactions among molecular recognition systems, neuronal activity, and glial regulation transform early neuronal connectivity into precise functional circuits during brain development. The cerebellum is a powerful model for studying these mechanisms due to its stereotyped and accessible circuitry. Two major excitatory afferent pathways-climbing fibers (CFs), which convey error-related signals to Purkinje cells (PCs), and mossy fibers (MFs), which transmit sensorimotor information via granule cells (GCs) and parallel fibers (PFs)-undergo strengthening, competition, and refinement during postnatal development. Synaptic specificity is established by general and pathway-specific organizers. The neurexin-neuroligin system broadly regulates synapse formation, while the neurexin-CBLN1-GluD2 complex specifies PF-PC synapses and C1qL1-BAI3 signaling stabilizes the dominant CF input during competitive refinement. CF-PC synapse elimination serves as a classic model of activity-dependent competition, where weaker inputs are removed through calcium-dependent mechanisms. In parallel, glial cells regulate synaptic maturation: microglia shape inhibitory environments, and Bergmann glia support glutamate homeostasis, dendritic organization, and synapse stability. PCs integrate CF and PF inputs and provide inhibitory output to the cerebellar nuclei, where convergent excitatory collaterals from CFs and MFs are combined with PC inhibition to generate cerebellar output. Together, these coordinated molecular, cellular, and circuit-level mechanisms establish the synaptic architecture underlying cerebellar computation, motor coordination, and adaptive learning, which are the central focus of this review. - Source: PubMed
Publication date: 2026/08/24
Ghiyamihoor FarshidAsemi Rad AzamMarzban Hassan - Cbln1 is a secreted synaptic organizer required for parallel fiber-Purkinje cell (PF-PC) synapse integrity, climbing fiber (CF) refinement, and cerebellar motor learning but has not previously been implicated in human disease. We identified bi-allelic CBLN1 missense variants (A63P and Y112C) in two unrelated families with early-onset cerebellar ataxia accompanied by oculomotor abnormalities, cerebellar atrophy, and variable cognitive delay. In heterologous cells, both variants showed reduced steady-state protein abundance, impaired maturation through the early secretory pathway, and little or no detectable secretion, resulting in markedly reduced extracellular CBLN1 availability. Consistently, cerebellar granule cells expressing CBLN1-Y112C failed to induce excitatory synapses onto glutamate receptor δ2 (GluD2)-expressing cells in vitro. A knockin mouse harboring Y112C lacked synaptic Cbln1 and recapitulated key features of Cbln1 deficiency, including disrupted PF-PC synapse organization, persistent CF multi-innervation, impaired PF-PC transmission, and long-term depression, and deficits in motor coordination and oculomotor learning. Notably, systemic delivery of an astrocyte-targeted adeno-associated virus expressing wild-type CBLN1 in adult mutant mice restored synaptic CBLN1 localization, cerebellar synaptic function, plasticity, and behavior. These findings establish CBLN1 deficiency as a cause of hereditary ataxia and identify extracellular CBLN1 replacement as a therapeutic strategy for a reversible cerebellar synaptopathy. - Source: PubMed
Publication date: 2026/09/02
Yamasaki TokiwaKakegawa WataruHayashi AyumiOgawa NaokoTakano TetsuyaMatsuda KeikoTakatsuto KumiAbdel-Hamid Mohamed SZaki Maha SGleeson Joseph GYuzaki Michisuke - The glutamate delta receptors GluD1 and GluD2 are part of the ionotropic glutamate receptor (iGluR) family; however, delta receptors differ from other iGluRs as they do not bind glutamate. These receptors have important and diverse functions in the brain and are known to be involved in various neurological diseases. Here, we report the monomeric X-ray crystal structure of the ligand-binding domain of rat GluD1 (rGluD1-LBD) with D-serine and Zn ions, determined at 2.8 Å resolution. By comparing the structures with Zn ions (rGluD1-LBD) and Ca ions (human, hGluD1-LBD), we show that species and crystallization differences do not affect intermediate domain closure and D-serine interactions with GluD1. Furthermore, examining the effect of replacing the Ca ions in the hGluD1-LBD dimer with Mg, Zn or Na ions did not reveal significant differences in the overall structure of the hGluD1-LBD for the different cations. We show that the cations were coordinated by the same residues, Glu527, Val530 and Asp531, and several water molecules. In the structure of hGluD1-LBD, Cl ions are present at the dimer interface and molecular dynamics (MD) simulations showed that removal of the ions leads to opening of the dimer, highlighting the importance of Cl ions in stabilizing the dimer. Finally, MD simulations of hGluD1-LBD and the Pro725 to Ser725 mutant, with and without D-serine in the binding site, suggest that Pro725 hinders full domain closure in GluD1, whereas an apparent synergistic effect of D-serine and mutation to Ser725 leads to a significant interlobe closure of the clamshell-like structure. - Source: PubMed
Publication date: 2026/08/16
Jørgensen Flemming SteenPedersen Emma GrosvaldNarayanan DilipFrydenvang Karla AKastrup Jette Sandholm - Chemical modification of proteins is an important tool for the development of protein-based therapeutics, a rapidly growing field in disease treatment. Currently, no universal approach exists for site-specifically introducing desired functionalities into proteins with minimal disruption. Here, we present a reactive peptide tag/probe pair system for site-specific covalent protein labeling, leveraging the interaction between a lysine-containing histidine tag (KH6 or H6K) and a binuclear nickel (II)-nitrilotriacetic acid (BisNi²+-NTA) probe conjugated to a lysine-reactive N-acyl-N-alkyl sulfonamide (NASA) electrophilic group. This chapter describes the system's validation, preparation of a glutamate receptor δ2 (GluD2) targeting nanobody-biotin conjugate, and its functional assessment via live-cell imaging of GluD2. The method offers a versatile, efficient approach for protein labeling applicable to protein engineering and targeted therapeutics. - Source: PubMed
Thimaradka VikramTamura TomonoriHamachi Itaru - Alzheimer's disease (AD) involves not only amyloid-β and tau pathology but synaptic dysfunction and impaired autophagy, though the underlying mechanisms and their relationship to AD progression are not well understood. Transsynaptic complexes involving presynaptic neurexins (Nrxn1/2/3), secreted cerebellins (Cbln1/2/3/4), and postsynaptic glutamate delta receptors (GluD1/2) play critical roles in organizing synapses and synaptic plasticity. Studies in pain models have reported that treatment with recombinant Cbln1 rescues AMPA glutamate receptor imbalance, promotes autophagy, and inhibits hyperexcitability and pain behaviors. Here we tested the novel hypothesis that dysregulation of Cbln-GluD-based transsynaptic complexes may occur in the brain of AD patients, providing insights into disease progression and potential avenues for therapeutic development. - Source: PubMed
Publication date: 2026/06/10
Hindle AshlyChen YongYin XianglingManczak MariaDecourt BorisNeugebauer Volker