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The authors find that the tumor suppressor Discs large (Dlg) links the Par (zeige AFG3L2 Proteine) complex component atypical Protein Kinase C (zeige PRKCZ Proteine) (aPKC) to the essential spindle orientation factor GukHolder (GukH).
The structure of dlg1 reveals that the core of the dimer is formed by a distinctive six-helix assembly, involving all three conserved helices from each subunit (monomer). The homodimer interface is extended by the C-terminal tail of the L27 (zeige RPL27A Proteine) domain of Dlg1, which forms a two-stranded antiparallel beta-sheet. The structure reconciles and provides a structural context for a large body of available mutational data.
Strikingly the absence of any of DLG proteins at the presynaptic terminal disrupts the clustering and localization of the calcium channel DmCa1A subunit (Cacophony), decreases the action potential-evoked release probability and alters short-term plasticity.
Exon junction complex (EJC) activity is indispensable for Wg signaling by maintaining an appropriate level of Dsh (zeige DVL2 Proteine) protein for Wg ligand reception in Drosophila. Genetic and biochemical experiments demonstrate that Dlg1 protein acts independently from its role in cell polarity to protect Dsh (zeige DVL2 Proteine) protein from lysosomal degradation.
Banderuola (Bnd) is a novel regulator of asymmetric cell division (ACD (zeige ACD Proteine)). The data place Bnd at the top of the hierarchy of the factors involved in ACD (zeige ACD Proteine), suggesting that its main function is mediating localization and function of Dlg tumor suppressor.
The inactivation of cellular cortex polarization is the most likely target of dlg inactivation in mitosis.
Loss of scrib, dlg and lgl had no effect on gonad formation, but Dlg and Scrib in the gonadal mesoderm acted critically in the somatic wrapping of the pole cells and the internal structure of the Drosophila embryonic gonads.
Gliotactin and Discs large are co-regulated to maintain epithelial integrity.
Hts (zeige APCDD1 Proteine) regulates Dlg targeting to the neuromuscular junction in muscle and the lateral membrane of epithelial cells.
Electron microscopy reveals that during metamorphosis the subsynaptic reticulum vacuolizes in the early stages of synapse dismantling, concomitant with diffuse localization of Dlg.
PSD95 was essential for Arc (zeige NOL3 Proteine) assembly into 1.5-MDa complexes and activity-dependent recruitment to excitatory synapses.
Results show the binding of PSD95 to GluN subunit 2A is modulated by CIN (zeige PDXP Proteine).
these data identify PSD95 nanoclusters as a basic structural unit, or building block, of excitatory synapses and their number characterizes synapse size and structural diversity
This study demonstrated that in Chronic social defeat stress leads to changes PSD-95 in hippocampus of young mice.
The authors present evidence that synGAP (zeige SYNGAP1 Proteine)-alpha1 regulates the composition of the postsynaptic density by restricting binding to the PDZ domains of PSD-95.
In Fmr1 (zeige FMR1 Proteine) KO neurons, Mdm2 (zeige MDM2 Proteine) is hyperphosphorylated, nuclear localized basally, and unaffected by MEF2 (zeige MEF2C Proteine) activation, which our data suggest due to an enhanced interaction with Eukaryotic Elongation Factor (zeige TSFM Proteine) 1alpha (EF1alpha), whose protein levels are elevated in Fmr1 (zeige FMR1 Proteine) KO. Expression of a dephosphomimetic of Mdm2 (zeige MDM2 Proteine) rescues PSD-95 ubiquitination, degradation and synapse elimination in Fmr1 (zeige FMR1 Proteine) KO neurons.
tested the effect of five targeted mouse mutations on the assembly of known PSD95 interactors, Kir2.3, Arc, IQsec2/BRAG1 and Adam22
Therefore, our study suggests that CREB and PSD95 are novel substrates of PERK, so inhibition of PERK phosphorylation using GSK2656157 would be beneficial against memory impairment after TBI.
PSD95 and SYP (zeige PTPN11 Proteine) may originate from the different sites, but they are closely related to the formation and maturation of synapse.
Expression levels of brain derived neurotrophic factor, postsynaptic density 95, and p-cyclic-AMP response element binding protein levels were significantly elevated in the testosterone (T) group, but flutamide reduced the T-induced effects in these biomarkers to control levels.
DNA methylation (zeige HELLS Proteine) of DLG4 and of human hippocampus and prefrontal cortex in major depression is unchanged in comparison to healthy individuals.
results suggest that rare missense mutations in the candidate PSD (zeige PSD Proteine) genes may increase susceptibility to SZ and/or ASD (zeige ARSD Proteine). These findings may strengthen the theory that rare, non-synonymous variants confer substantial genetic risks for these disorders
in postsynaptic densities, PSD95 palmitoylation, conformation, and its interactions are dynamic when associated with AMPARs and more stable when associated with NMDARs
a dual role for PSD-95 in stabilizing synaptic NMDARs by binding directly to GluN2B (zeige GRIN2B Proteine) but also by promoting synaptic exclusion and degradation of the negative regulator STEP61.
the authors integrate molecular and imaging data from animal models and preterm infants, and find that microglial expression of DLG4 plays a role.
Phosphorylation at Y397 induced a significant increase in affinity for stargazing. The strategy presented here to generate site-specifically phosphorylated PDZ domains provides a detailed understanding of the role of phosphorylation in the regulation of PSD95 interactions.
This study demonstrated that a significant decrease in the protein level of PSD-95 in major depression disorder.
These results indicate that PKC (zeige PRRT2 Proteine) promotes synaptogenesis by activating PSD-95 phosphorylation directly through JNK1 (zeige MAPK8 Proteine) and calcium/calmodulin-dependent kinase II and also by inducing expression of PSD-95 and synaptophysin (zeige SYP Proteine).
The differences in cortical NMDAR (zeige GRIN1 Proteine) expression and post-synaptic density protein 95 are present in psychiatric disorders and suicide completion and may contribute to different responses to ketamine.
Mutation C>T at the rs13331 in the PSD95 gene is strikingly associated with an increased risk of autism spectrum disorders.
This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene.
, disc large
, discs large
, disk large
, lethal(1)benign wing imaginal disc neoplasm
, lethal(1)discs large
, lethal(2)discs large
, discs, large homolog 4
, postsynaptic density protein 95
, disks large homolog 4
, PSD-95 alpha 2b
, PSD-95 beta
, discs large homolog 4
, synapse-associated protein 90
, synapse-associated protein SAP90
, Tax interaction protein 15
, post-synaptic density protein 95