| 1996 |
SAP102 interacts in vivo with NMDA receptor complexes: antibodies against NMDA receptors co-immunoprecipitate SAP102 from rat brain synaptosomes, and all three PDZ domains of SAP102 bind the cytoplasmic tail of NR2B in vitro, linking NMDA receptors to the postsynaptic cytomatrix. |
Co-immunoprecipitation from rat brain synaptosomes; in vitro binding with recombinant proteins containing NR2B carboxy-terminal tail |
Neuron |
High |
8702950 8780649
|
| 1996 |
SAP102 specifically interacts with the NMDA receptor complex (but not AMPA receptor subunit GluR1) via the last 20 amino acids of the NR2 subunit C-terminal tail, as demonstrated in cortical synaptic plasma membranes. |
Co-immunoprecipitation from cortical synaptic plasma membranes; hexahistidine fusion protein overlay; synthetic peptide interaction assay |
The Journal of biological chemistry |
High |
8702950
|
| 1997 |
NE-dlg/SAP102 interacts with the carboxyl-terminal region of the APC tumor suppressor protein, as revealed by yeast two-hybrid screening and in vitro binding assays, and is expressed in non-proliferating neuronal and endocrine cells. |
Yeast two-hybrid screening; in vitro binding assay |
Oncogene |
Medium |
9188857
|
| 1997 |
SAP102 functionally substitutes for Drosophila DlgA: when expressed in dlg-1 mutant flies, SAP102 suppresses tumor formation and restores synaptic bouton morphology at larval neuromuscular junctions, requiring neuronal expression. |
Heterologous expression in Drosophila dlg-1 mutants; morphological analysis of synaptic boutons |
Mechanisms of development |
Medium |
9152008
|
| 1999 |
NE-dlg/SAP102 interacts with calmodulin in a Ca2+-dependent manner (Kd ~44 nM) via a basic alpha-helix region near the SH3 domain, and also interacts with the GUK-like domain of PSD-95/SAP90 in the presence of Ca2+/calmodulin; Ca2+/calmodulin binding does not modulate the PDZ–NR2B interaction. |
Surface plasmon resonance; pull-down assay; yeast two-hybrid screening |
The Journal of biological chemistry |
High |
10026200
|
| 1999 |
A novel SAP102-binding protein, p51-nedasin (predominantly the S splice form), interacts with SAP102 in cell bodies and interferes with the association between SAP102 and NMDA receptor NR2B in vitro, suggesting a regulatory role in NMDA receptor clustering at synapses. |
Yeast two-hybrid; co-immunoprecipitation; in vitro competition assay |
The Journal of biological chemistry |
Medium |
10542258
|
| 2000 |
Overexpression of NE-dlg/SAP102 in cancer cell lines induces growth suppression, impairment of cell adhesion, and downregulation of beta-catenin through an APC-independent pathway; the PDZ domains of NE-dlg are required for these effects. |
Overexpression in cancer cell lines; domain deletion analysis; Western blotting for beta-catenin |
International journal of cancer |
Medium |
10797259
|
| 2001 |
By electron microscopic immunocytochemistry, SAP102 is localized at postsynaptic densities of spines but also diffusely along presynaptic membranes and in axonal cytoplasm of rat visual cortex, suggesting roles in both receptor anchoring at synapses and receptor shuttling between nonsynaptic and synaptic sites. |
Electron microscopic immunocytochemistry (quantitative EM-ICC) in rat visual cortex |
Synapse |
Medium |
11309840
|
| 2003 |
The proline-rich regions of Pyk2 bind the SH3 domain of SAP102 (and PSD-95), recruiting Pyk2 to the NMDA receptor complex; the intramolecular SH3–GK domain interaction in SAP102 restricts Pyk2 binding to the SH3 domain, revealed when the GK domain is removed. |
Co-immunoprecipitation; pull-down; immunofluorescence co-localization; domain deletion analysis |
The Journal of biological chemistry |
Medium |
12576483
|
| 2005 |
mPins (mammalian partner of inscuteable) interacts with SAP102 and functions in forming the NMDAR-MAGUK complex; mPins enhances trafficking of SAP102 and NMDARs to the plasma membrane, and dominant-negative mPins or siRNA knockdown of mPins decreases SAP102 in dendrites and reduces NMDAR surface expression. |
Co-immunoprecipitation; siRNA knockdown; dominant-negative expression; surface expression assays in neurons |
Nature cell biology |
High |
16299499
|
| 2008 |
SAP102 mediates synaptic trafficking of both AMPA and NMDA receptors during synaptogenesis; after synaptogenesis, PSD-95 assumes these functions. This temporal division was established by in utero electroporation with dual whole-cell electrophysiology at two developmental stages. |
In utero electroporation; dual whole-cell patch-clamp electrophysiology at distinct developmental stages; knockout mice |
Proceedings of the National Academy of Sciences of the United States of America |
High |
19104036
|
| 2011 |
SAP102 contains a novel N-terminal NMDA receptor binding site specific for NR2B that is PDZ-domain independent and is regulated by alternative splicing; the N-terminal insert splice variant promotes dendritic spine lengthening and synapse formation at long spines, and blocking NMDA receptor activity prevents this spine lengthening. |
Co-immunoprecipitation; domain mapping; shRNA knockdown; morphological analysis of dendritic spines; pharmacological NMDA receptor blockade |
The Journal of neuroscience |
High |
21209193
|
| 2011 |
Dlg3 contributes to apical-basal polarity and tight junction formation in polarized epithelial cells; Dlg3 recruits E3 ubiquitin ligases Nedd4 and Nedd4-2 through its PPxY motifs, leading to Dlg3 monoubiquitination, apical membrane recruitment, and tight junction consolidation. |
Affinity purification/mass spectrometry of Dlg3 complexes; co-immunoprecipitation; mouse knockout; immunofluorescence; ubiquitination assays |
Developmental cell |
High |
21920314
|
| 2011 |
SAP102 PDZ domain ligand-binding is not essential for its own synaptic clustering; however, direct PDZ-mediated binding of NMDARs to SAP102 is required for efficient synaptic targeting of NMDA receptor subunits GluN2A and GluN2B. |
Expression of SAP102 PDZ-binding-deficient mutants in hippocampal neurons; co-expression with GluN2A/GluN2B; synaptic clustering analysis |
Neuroscience letters |
Medium |
23178474
|
| 2012 |
SAP102 mediates synaptic clearance of GluN2B-containing NMDARs through a secondary non-PDZ interaction; two critical residues on GluN2B responsible for non-PDZ binding to SAP102 were identified, and mutation of these residues or SAP102 knockdown rescues defective surface/synaptic expression of PDZ-binding-deficient GluN2B. |
Mutagenesis of GluN2B residues; SAP102 siRNA knockdown; surface biotinylation; electrophysiology |
Cell reports |
High |
23103165
|
| 2012 |
SAP102 binds to the C-terminal part of neurobeachin (Nbea) containing the DUF, PH, BEACH, and WD40 domains; a mutation in Nbea's PH domain that disrupts its PH-BEACH interaction abolishes SAP102 binding. |
Mass spectrometry identification from mouse brain; co-immunoprecipitation in heterologous cells; domain mapping with mutations |
PloS one |
Medium |
22745750
|
| 2013 |
SAP102 regulates cortical synapse development through EphB and PAK signaling: SAP102 co-immunoprecipitates EphB2 and Kalirin-7 in neonatal cortex; SAP102 knockdown reduces EphB surface expression, prevents actin reorganization and synapse formation in response to ephrinB, and downregulates PAK activity. |
Lentivirus shRNA knockdown; co-immunoprecipitation; surface expression analysis; EphB activation assays; actin cytoskeleton analysis |
The Journal of neuroscience |
High |
23486974
|
| 2014 |
SAP102 interacts with the A2A adenosine receptor C-terminus (via the SH3 and GK domains of SAP102); SAP102 overexpression prevents the A2A receptor from accessing a compartment with restricted (slow) mobility, dependent on a DVELL motif in the A2A receptor C-terminus. |
Single particle tracking (quantum dot); co-immunoprecipitation; hidden Markov model analysis of diffusion; dominant-negative fragment expression |
The Journal of biological chemistry |
Medium |
24509856
|
| 2015 |
Synaptic localization of SAP102 is regulated by C-terminal alternative splicing: the I2 splice variant (insert between SH3 and GK domains) is highly enriched at dendritic spines and is developmentally regulated; knockdown of I2-containing SAP102 isoforms differentially affects NMDAR surface expression in a subunit-specific manner. |
Expression of splice variant constructs; shRNA knockdown of specific isoforms; surface biotinylation; spine morphology analysis |
The Journal of biological chemistry |
Medium |
25555912
|
| 2017 |
SAP102 synaptic targeting is regulated by phosphorylation at serine 632 by casein kinase II (CK2): Ser632 phosphorylation increases synaptic enrichment of SAP102 and decreases its mobility; elevation of synaptic activity suppresses Ser632 phosphorylation and reduces synaptic enrichment. |
In vitro kinase assay; phospho-specific analysis in heterologous cells and neurons; FRAP; activity manipulation |
Molecular neurobiology |
Medium |
29282697
|
| 2018 |
SAP102 regulates synaptic AMPAR function through a CNIH-2 (cornichon-2)-dependent mechanism: SAP102 rescues AMPAR eEPSCs and increases AMPAR mEPSC decay time upon PSD-95 knockdown, and this rescue requires the AMPAR auxiliary subunit cornichon-2. |
Molecular replacement (shRNA KD of PSD-95 + SAP102 expression); whole-cell patch-clamp electrophysiology; cornichon-2 knockdown |
Journal of neurophysiology |
Medium |
30067114
|
| 2020 |
MIAT lncRNA promotes methylation of CpG islands in the DLG3 promoter by binding to DNMT1, DNMT3A, and DNMT3B, suppressing DLG3 expression; DLG3 binds MST2 and regulates LATS1, preventing nuclear translocation of YAP to activate the Hippo pathway in breast cancer cells. |
MS-PCR; RIP assay; dual luciferase reporter; siRNA knockdown; co-immunoprecipitation; in vivo tumor models |
Cellular signalling |
Medium |
32593652
|
| 2023 |
COP1 E3 ubiquitin ligase binds DLG3 protein and enhances its ubiquitination, promoting glioma cell proliferation, invasion, and migration; DLG3 silencing reverses the inhibitory effect of COP1 knockdown. |
Co-immunoprecipitation; ubiquitination assay (MG132 treatment); siRNA knockdown; CCK-8, EdU, Transwell assays |
Neurological research |
Medium |
37356109
|
| 2023 |
Sec8 (exocyst subunit) preferentially binds PDZ2 over PDZ1 and PDZ3 of SAP102 via its C-terminal ITTV motif; a 14-residue 'spacer' bridging ITTV to the Sec8 core is essential, as its deletion abolishes SAP102 binding. |
2.5 Å crystal structure of Sec8 C-terminus; in vitro binding assays; domain deletion analysis; molecular modeling |
Frontiers in cell and developmental biology |
High |
37849738
|
| 2024 |
JNK3 directly phosphorylates SAP102, negatively regulating its synaptic dynamics; JNK activity modulates SAP102 and kainate receptor subunit GluK2 surface expression and trafficking to postsynaptic sites in a neuronal context. |
In vitro phosphorylation assay; live-cell imaging; pharmacological JNK inhibition; surface expression assays |
The Journal of biological chemistry |
Medium |
38582451
|
| 2024 |
SAP102 accumulates in high-density subsynaptic nanoclusters that are smaller and denser than PSD-95 nanoclusters; only a subset of SAP102 nanoclusters co-organize with PSD-95, revealing distinct MAGUK nanodomains within individual synapses that differentially associate with the presynaptic release protein Munc13-1. |
DNA-PAINT super-resolution microscopy in cultured rat neurons |
The Journal of neuroscience |
Medium |
38777601
|
| 2016 |
Genetic deletion of SAP102 (Dlg3 knockout) in mice reduces the number of thalamocortical axons innervating the somatosensory cortex, causes a transient speeding of NMDA receptor kinetics during the critical period without reducing GluN2B-mediated transmission, and reduces divergence of TC connectivity after the critical period. |
Dlg3 knockout mouse; in vivo and in vitro electrophysiology; axon quantification |
Human molecular genetics |
High |
27466188
|
| 2016 |
A 5' UTR duplication variant in DLG3 (dupG, 7 nt upstream of the start codon) attenuates protein translation without affecting mRNA levels, causing intellectual disability; demonstrated by dual luciferase reporter assay and reduced protein in patient blood cells. |
Dual luciferase reporter assay; Western blot of patient-derived cells; mRNA level analysis |
European journal of human genetics |
Medium |
27222290
|