Affinage

MPDZ

Multiple PDZ domain protein · UniProt O75970

Length
2070 aa
Mass
221.6 kDa
Annotated
2026-04-28
67 papers in source corpus 38 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MPDZ (MUPP1) is a multivalent PDZ-domain scaffolding protein that organizes signaling complexes at tight junctions, synapses, and gap junctions to regulate epithelial barrier integrity, neuronal plasticity, receptor signaling, and developmental patterning. Its 13 PDZ domains simultaneously engage claudins, JAM, and CAR at tight junctions to maintain paracellular barrier function — loss of MPDZ mislocalizes claudin-4 to lysosomes and increases epithelial permeability — while in neurons it assembles a SynGAP–CaMKIIα complex whose Ca²⁺/calmodulin-dependent disassembly controls p38 MAPK inactivation and AMPAR potentiation (PMID:11689568, PMID:18840681, PMID:15312654). MPDZ scaffolds GPCR signaling by coupling receptors (MT1, GABA_B R2, 5-HT2C, hSSTR3) to Gi proteins and stabilizing receptor expression, and it bridges Notch ligands DLL1/DLL4 with nectin-2 to enable Notch-dependent angiogenesis (PMID:18378672, PMID:17145756, PMID:29620522). Loss-of-function mutations in MPDZ cause autosomal recessive congenital hydrocephalus through disrupted ependymal and choroid plexus barrier integrity, with diminished Pals1, elevated RhoA activity, and massively increased choroid plexus permeability (PMID:23240096, PMID:28500065, PMID:30518636).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 Medium

    Identification of MPDZ as a 13-PDZ-domain protein interacting with the 5-HT2C receptor established its scaffolding architecture and first receptor partnership, answering whether cells possess multi-PDZ adaptors that could simultaneously bind multiple partners.

    Evidence Yeast two-hybrid screen with 5-HT2C C-terminus in human brain library

    PMID:9537516

    Open questions at the time
    • Single interaction method (Y2H) without endogenous validation
    • No cellular function assigned
  2. 2001 High

    Localization of MUPP1 to tight junctions through direct binding of claudin-1 (PDZ10) and JAM (PDZ9) revealed MPDZ as a core TJ scaffold, redefining it from a receptor adaptor to a junctional organizer.

    Evidence Y2H, in vitro binding, immunofluorescence, and immunoelectron microscopy in polarized MDCK cells

    PMID:11150294 PMID:11689568

    Open questions at the time
    • Functional consequence of MUPP1 loss on barrier integrity not yet tested
    • Redundancy with PATJ not addressed
  3. 2000 Medium

    Viral oncoproteins (Ad9 E4-ORF1, HPV-18 E6) targeting MUPP1 for sequestration or degradation implied a tumor-suppressive role, connecting MPDZ to proliferation control before direct evidence in cancer pathways existed.

    Evidence Co-IP and subcellular localization with wild-type and mutant viral proteins

    PMID:11000240

    Open questions at the time
    • No direct measurement of MUPP1 effect on proliferation
    • Endogenous tumor suppressor mechanism not identified
  4. 2004 High

    Assembly of a SynGAP–CaMKIIα ternary complex on MUPP1 at synapses, with Ca²⁺/CaM-dependent disassembly driving p38 MAPK inactivation and AMPAR potentiation, established MPDZ as a critical scaffold for synaptic plasticity.

    Evidence Co-IP, competitive peptide disruption, siRNA knockdown, electrophysiology, and AMPAR cluster analysis in hippocampal neurons

    PMID:15312654

    Open questions at the time
    • In vivo behavioral consequence of MPDZ loss at synapses not tested
    • Structural basis of ternary complex unknown
  5. 2004 High

    Positional cloning of Mpdz as the quantitative trait gene for alcohol and pentobarbital withdrawal seizures in mice linked MPDZ scaffolding to CNS excitability and pharmacogenetics.

    Evidence Congenic strain analysis and positional cloning within <1 cM interval on mouse chromosome 4

    PMID:15208631

    Open questions at the time
    • Molecular mechanism connecting MPDZ variants to seizure threshold not identified
    • Human MPDZ variants in alcohol withdrawal not tested
  6. 2008 High

    Demonstration that MUPP1 controls claudin-4 targeting to TJs (preventing lysosomal mislocalization) and is required for epithelial barrier maintenance under hypertonic stress provided the first mechanistic link between MUPP1 and cargo sorting at junctions.

    Evidence RNAi silencing, Co-IP, immunofluorescence, lysosome inhibitor rescue, and TER measurement in IMCD3 cells

    PMID:17690246 PMID:18840681

    Open questions at the time
    • Whether MUPP1 directly prevents claudin ubiquitination or acts through an intermediary unknown
    • In vivo renal phenotype of MPDZ loss not assessed
  7. 2008 High

    High-affinity binding of MUPP1 PDZ10 to the MT1 melatonin receptor (Kd ~4 nM), required for Gi coupling but not receptor trafficking, established MPDZ as an essential scaffold for GPCR–G-protein assembly rather than merely a localizing factor.

    Evidence ITC binding measurements, Co-IP from native ovine pars tuberalis, peptide disruption of Gi signaling

    PMID:18378672

    Open questions at the time
    • Whether MUPP1 scaffolds a pre-coupled receptor–Gi complex or facilitates dynamic coupling unknown
    • Structural basis of PDZ10-mediated Gi coupling not resolved
  8. 2009 High

    Functional redundancy and distinction between MUPP1 and PATJ at tight junctions was clarified: both share binding partners (JAM1, Pals1, Par6), but only PATJ is indispensable for TJ establishment and epithelial polarization, positioning MUPP1 as a modulatory rather than essential TJ scaffold in standard culture.

    Evidence RNAi knockdown, Co-IP, TER measurement in MDCK cells

    PMID:19255144

    Open questions at the time
    • In vivo tissue-specific contexts where MUPP1 becomes essential (e.g., ependyma) not yet examined
    • Whether MUPP1 and PATJ compete for the same binding sites on Pals1 not resolved
  9. 2013 Medium

    Identification of a loss-of-function MPDZ mutation in families with autosomal recessive congenital hydrocephalus established MPDZ as a human disease gene, linking its junctional scaffolding to brain barrier integrity.

    Evidence Autozygosity mapping and linkage analysis with truncating mutation in two consanguineous families

    PMID:23240096

    Open questions at the time
    • Cellular mechanism of hydrocephalus not determined at this point
    • No functional rescue or animal model confirmation
  10. 2017 High

    Conditional Mpdz knockout mice recapitulated hydrocephalus through progressive ependymal barrier failure with diminished Pals1 and elevated RhoA activity, establishing a mechanistic pathway from MPDZ loss to barrier breakdown and aqueductal stenosis.

    Evidence Global and Nestin-Cre conditional KO mice, MRI, RhoA activity assay, in vitro barrier assays

    PMID:28500065

    Open questions at the time
    • Whether Pals1 loss is cause or consequence of ependymal breakdown not resolved
    • Therapeutic potential of RhoA inhibition not tested
  11. 2018 High

    MPDZ was shown to scaffold Notch ligands DLL1/DLL4 with nectin-2 at endothelial junctions; its loss impaired Notch signaling and increased vessel sprouting, extending MPDZ function from epithelial barriers to vascular morphogenesis.

    Evidence Co-IP, conditional endothelial KO in mice, hindbrain vessel sprouting assay, Notch reporter

    PMID:29620522

    Open questions at the time
    • Whether MPDZ regulates Notch signaling in non-endothelial contexts unknown
    • Which PDZ domains mediate DLL interactions not fully mapped
  12. 2019 High

    MRI-based demonstration that Mpdz-null choroid plexus is hyperpermeble, with 53-fold elevated CSF protein, pinpointed the choroid plexus as a primary site of MPDZ-dependent barrier failure in hydrocephalus.

    Evidence Contrast-enhanced MRI, CSF comparative proteomics, electron microscopy in KO mice

    PMID:30518636

    Open questions at the time
    • Relative contributions of ependymal vs. choroid plexus permeability to hydrocephalus not dissected
    • Transcytosis mechanism suggested by EM not molecularly characterized
  13. 2021 Medium

    MPDZ was found to activate Hippo-YAP signaling by stabilizing MST1 and interacting with LATS1 to promote YAP phosphorylation, providing a molecular mechanism for the tumor-suppressive role first implied by viral oncoprotein targeting.

    Evidence Co-IP with LATS1, Western blot for phospho-YAP, MPDZ KO and overexpression in cell lines and xenograft mice

    PMID:34108620

    Open questions at the time
    • Single-lab finding; independent replication needed
    • Direct binding interface between MPDZ and LATS1 not structurally resolved
    • Whether Hippo activation is relevant in ependymal/choroid plexus cells unknown
  14. 2023 Medium

    Loss of MPDZ (with PATJ) in preimplantation embryos disrupted apical polarity, tight junctions, and Hippo pathway activity in outer cells, suppressing trophectoderm specification — connecting MPDZ scaffolding to the earliest mammalian lineage decision.

    Evidence Zygote siRNA microinjection, immunofluorescence, blastocyst assessment

    PMID:37318097

    Open questions at the time
    • Combined MPDZ+PATJ knockdown does not distinguish individual contributions
    • Whether MPDZ acts through Hippo directly or via polarity disruption in this context is unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how the 13 PDZ domains of MPDZ are coordinately regulated to achieve context-specific complex assembly, what post-translational modifications control MPDZ activity, and whether MPDZ dysfunction contributes to human neuropsychiatric phenotypes beyond hydrocephalus.
  • No full-length MPDZ structure available
  • Post-translational regulation of MPDZ largely uncharacterized
  • Human genetic studies for neuropsychiatric or vascular phenotypes lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5
Localization
GO:0005886 plasma membrane 5 GO:0005829 cytosol 2
Pathway
R-HSA-1500931 Cell-Cell communication 5 R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 2
Partners
CAMK2ACLDN1DLL4F11RGABBR2LATS1MTNR1ASYNGAP1
Complex memberships
CRB3-Pals1-PATJ/MUPP1 apical polarity complexSynGAP-CaMKIIα-MUPP1 synaptic complexTight junction scaffold complex (claudin-JAM-CAR-MUPP1)

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 MPDZ/MUPP1 was identified as a novel protein containing 13 PDZ domains that interacts with the C-terminal domain of the 5-HT2C serotonin receptor, identified via yeast two-hybrid screening. It has no obvious catalytic domain, suggesting a scaffolding/adaptor role. Yeast two-hybrid system FEBS letters Medium 9537516
2001 MUPP1 is concentrated at tight junctions in polarized epithelial cells through direct binding to claudin-1 (via PDZ10 domain) and junctional adhesion molecule (JAM, via PDZ9 domain), functioning as a multivalent scaffold protein at TJs. Yeast two-hybrid, in vitro binding assays with recombinant MUPP1, immunofluorescence confocal microscopy, immunoelectron microscopy The Journal of biological chemistry High 11689568
2001 The C-terminus of the 5-HT2C receptor selectively interacts with PDZ10 of MUPP1 via its SXV motif; 5-HT2A and 5-HT2B receptors also bind MUPP1 PDZ domains in vitro. The interaction triggers a conformational change within MUPP1. Yeast two-hybrid, co-immunoprecipitation from transfected COS-7 cells and rat choroid plexus, immunocytochemistry, in vitro binding The Journal of biological chemistry High 11150294
2000 Ad9 E4-ORF1 oncoprotein aberrantly sequesters MUPP1 within the cytoplasm, while HPV-18 E6 oncoprotein targets MUPP1 for degradation; both interactions are mediated by the viral PDZ domain-binding motifs. This implicates MUPP1 in negative regulation of cellular proliferation. Co-immunoprecipitation, subcellular localization studies with wild-type and mutant viral proteins Journal of virology Medium 11000240
2000 MUPP1 binds to the cytoplasmic C-terminus of the NG2 chondroitin sulfate proteoglycan via its PDZ1 region; interaction demonstrated in cell lysates and requires the C-terminal half of the NG2 cytoplasmic domain. Yeast two-hybrid, GST pull-down assay, co-immunoprecipitation from cell extracts Journal of cellular biochemistry Medium 10967549
2000 MUPP1 binds to c-Kit via its PDZ10 domain through the c-Kit C-terminal sequence; kinase-negative c-Kit interacts more strongly with MUPP1 than wild-type, while constitutively activated D816V-Kit does not bind MUPP1. Deletion of the PDZ-binding motif drastically reduces c-Kit tyrosine kinase activity. Co-immunoprecipitation, yeast two-hybrid, domain mapping with mutants FEBS letters Medium 11018522
2002 TAPP1 and TAPP2 interact with MUPP1 PDZ domains 10 and 13 through their C-terminal amino acids; endogenous TAPP1 co-immunoprecipitates endogenous MUPP1 from 293 cells. TAPP1 translocates to the plasma membrane upon PtdIns(3,4)P2 generation, potentially recruiting MUPP1 to the membrane. Co-immunoprecipitation of endogenous proteins, domain mapping, membrane translocation assay with wortmannin inhibition The Biochemical journal Medium 11802782
2003 Claudin-8 binds MUPP1 through its PDZ9 domain; both co-localize and co-immunoprecipitate at tight junctions in MDCK cells. Over-expression of MUPP1 reduces epithelial paracellular conductance. Yeast two-hybrid, co-immunoprecipitation, immunolocalization, transepithelial electrical resistance measurement Cellular and molecular biology Medium 12839333
2004 MUPP1 forms a synaptic complex with SynGAP and CaMKII in hippocampal neurons; SynGAP and CaMKII are brought together by direct physical interaction with MUPP1 PDZ domains. Ca2+/CaM binding to CaMKII dissociates it from the MUPP1 complex, and Ca2+ via NMDAR drives SynGAP dephosphorylation, leading to p38 MAPK inactivation and potentiation of synaptic AMPA responses. Co-immunoprecipitation, peptide disruption of complex, siRNA knockdown, electrophysiology, AMPAR cluster counting Neuron High 15312654
2004 CAR (coxsackievirus and adenovirus receptor) interacts with MUPP1 PDZ domain 13 via its C-terminal PDZ-binding motif within the tight junction; CAR expression is required for proper MUPP1 localization at tight junctions. Yeast two-hybrid, co-immunoprecipitation, co-localization, in vitro binding, siRNA knockdown of CAR The Journal of biological chemistry High 15364909
2004 Mpdz is identified as a quantitative trait gene for drug (alcohol and pentobarbital) withdrawal seizures in mice via positional cloning within a <1 cM interval on mouse chromosome 4. Positional cloning, congenic strain analysis, sequence analysis Nature neuroscience High 15208631
2006 MUPP1 functions as a lipid raft-associated scaffolding protein in the acrosomal region of mammalian spermatozoa, controlling initial tethering and docking of the acrosomal vesicle during exocytosis; syntaxin 2 participates in the final acrosomal fusion step. Inhibitory antibody loading in permeabilized sperm, photosensitive Ca2+ chelator, immunogold electron microscopy, detergent-insoluble membrane fractionation Journal of cellular physiology Medium 17894389
2006 MUPP1 and Patj share binding partners including JAM1, ZO-3, Pals1, Par6, and nectins; both localize to tight junctions, but only Patj (not MUPP1) is indispensable for TJ establishment and epithelial polarization. Pals1 has higher affinity for Patj than MUPP1 and is key for Patj's function in activating the Par6-aPKC complex. Co-immunoprecipitation, RNAi knockdown, transepithelial resistance measurement, immunofluorescence Molecular and cellular biology High 19255144
2006 GABA(B)R2 C-terminus interacts with Mupp1 PDZ13; disruption of this interaction by point mutation or siRNA knockdown of Mupp1 decreases GABA(B) receptor stability and attenuates the duration of GABA(B) receptor signaling. PDZ domain array screen, biochemical co-immunoprecipitation, siRNA knockdown, receptor stability and signaling assays The Journal of biological chemistry High 17145756
2007 MUPP1 interacts with angiomotin (Amot), JEAP/Amot-like 1, and MASCOT/Amot-like 2 (Amot/JEAP family) via PDZ2/3 domains at tight junctions and apical membranes; however, PDZ-binding motifs of Amot/JEAP family are not required for their TJ localization, and dominant-negative MUPP1 does not affect their distribution. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence, biochemical fractionation Genes to cells Medium 17397395
2007 MUPP1 is upregulated by hypertonicity in kidney IMCD3 cells and is required for maintenance of tight epithelial barrier function; silencing of MUPP1 reduces transepithelial resistance by 24%. Antibody array proteomics, qPCR, Western blot, stable RNAi silencing, transepithelial resistance measurement Proceedings of the National Academy of Sciences Medium 17690246
2008 MUPP1 binds the MT1 melatonin receptor via PDZ10 and the receptor's C-terminal DSV motif (Kd ~4 nM); this interaction is independent of receptor activation but is required for MT1-Gi coupling and Gi-mediated signaling, without affecting receptor localization or trafficking. Co-immunoprecipitation, isothermal titration calorimetry, PDZ domain mapping, peptide disruption, signaling assays The Journal of biological chemistry High 18378672
2008 MUPP1 interacts with hSSTR3 (human somatostatin receptor 3) via its PDZ domains; this interaction targets hSSTR3 to tight junctions, enabling somatostatin to regulate transepithelial permeability in a pertussis toxin-sensitive (Gi-dependent) manner. Co-immunoprecipitation, immunolocalization, transepithelial resistance/permeability assay, pertussis toxin treatment FEBS letters Medium 19071123
2008 MUPP1 is upregulated by hypertonicity in kidney IMCD3 cells and correctly localizes claudin-4 to tight junctions; in MUPP1-silenced cells, claudin-4 is mistargeted to lysosomes, reducing TER equivalently to claudin-4 silencing. Co-immunoprecipitation, RNAi silencing, immunofluorescence, lysosome inhibitor rescue, transepithelial resistance measurement Proceedings of the National Academy of Sciences High 18840681
2008 MUPP1 localizes at oligodendrocyte-astrocyte gap junctions with Cx47; ablation of Cx47 leads to loss of MUPP1 (and ZONAB) at these junctions, while Cx32 ablation does not affect MUPP1, demonstrating Cx47-dependent targeting of MUPP1 to O/A gap junctions. Immunofluorescence, knockout mouse analysis (Cx47-KO and Cx32-KO) The European journal of neuroscience Medium 18973575
2008 Tech (neuronal RhoA GEF) binds MUPP1 PDZ10 and PDZ13 via its C-terminal PDZ ligand; endogenous Tech co-precipitates with MUPP1 from hippocampal and cortical brain extracts, and both co-localize near synapses in cortical neurons. Yeast two-hybrid, co-transfection in HEK293 cells, co-immunoprecipitation from brain extracts, immunostaining Journal of neurochemistry Medium 18537874
2009 CaMKIIα co-localizes with MUPP1 in the acrosomal region of spermatozoa and selectively binds to MUPP1 PDZ domains 10-11. CaMKII inhibition or competitive displacement of CaMKIIα from PDZ10-11 increases spontaneous acrosomal exocytosis; Ca2+/calmodulin releases CaMKIIα from MUPP1, dynamically regulating acrosomal secretion. Co-immunoprecipitation, CaMKII inhibitor treatment, competitive peptide displacement, acrosome reaction assay Journal of cell science High 19934217
2009 MUPP1 interacts with renal K+ channel Kir4.2 via its C-terminal PDZ motif; co-expression of MUPP1 reduces cell surface expression of Kir4.2 and decreases whole-cell K+ currents in Xenopus oocytes. Yeast two-hybrid, reciprocal co-immunoprecipitation from rat kidney cortex, cell surface biotinylation, Xenopus oocyte electrophysiology, immunofluorescence American journal of physiology. Renal physiology High 19420109
2011 AF6 and MUPP1 are components of neuronal gap junctions in rodent brain, co-localizing with Cx36; MUPP1 interacts with Cx36 via the 10th PDZ domain of MUPP1 recognizing the C-terminus PDZ interaction motif of Cx36. This positions MUPP1 to potentially anchor CaMKII at electrical synapses. Co-immunoprecipitation, GST pull-down, immunofluorescence colocalization The European journal of neuroscience Medium 22211808
2012 CADM1/SynCAM1 C-terminal peptide associates with MUPP1 PDZ1-5 in the cerebellum; MUPP1 also interacts with GABBR2 at PDZ13. Loss of CADM1 in KO mice increases GABBR2 protein (but not mRNA) levels, suggesting that the CADM1-MUPP1-GABBR2 complex stabilizes GABBR2. Co-immunoprecipitation, pull-down assay, immunofluorescence, knockout mouse analysis Journal of neurochemistry Medium 22994563
2013 MUPP1 expression inversely correlates with PATJ protein levels by acting on stabilization of the PATJ/PALS1 complex; MUPP1 depletion leads to increased PATJ localized at the migrating front with increased PAR3 recruitment, indicating MUPP1 regulates polarity complex balance. RNAi depletion, co-immunoprecipitation, immunofluorescence Experimental cell research Medium 23880463
2013 Loss-of-function mutation in MPDZ causes severe congenital hydrocephalus (communicating type) following autosomal recessive inheritance, establishing MPDZ as a congenital hydrocephalus disease gene. Autozygosity mapping, linkage analysis, direct sequencing of candidate genes Journal of medical genetics Medium 23240096
2014 MUPP1 organizes a macromolecular signaling complex in mouse olfactory sensory neurons; disruption of the PDZ signaling complex by inhibitory peptide strongly impairs odor responses and alters activation and termination kinetics. Co-immunoprecipitation, inhibitory peptide disruption, electrophysiological recording of olfactory sensory neurons Journal of cell science Medium 24652834
2014 Neurexin 1 (and neurexins 2 and 3) interact with MUPP1 through its PDZ domain; MUPP1 and neurexin 1 co-localize in cultured cells. Yeast two-hybrid, co-localization in cultured cells Bioscience, biotechnology, and biochemistry Low 25036961
2015 CASPR2 interacts with GPR37 via MUPP1 as a bridge; CASPR2 binds MUPP1 PDZ3, GPR37 binds MUPP1 PDZ11. The ASD-associated GPR37(R558Q) mutant shows reduced MUPP1 interaction and is not transported to the cell surface, while wild-type GPR37 is transported to dendrites and synapses by MUPP1. Co-immunoprecipitation from mouse brain, transfection experiments, immunofluorescence in hippocampal neurons, PDZ domain mapping Journal of neurochemistry Medium 25977097
2015 Crystal structure of MUPP1 PDZ4 domain resolved at 1.6 Å; the domain contains three α-helices and six β-strands, with a binding pocket formed by GLGI motif, L562/A564 on β-strand B, and H605/V608/L612 on α-helix B. X-ray crystallography, size-exclusion chromatography Acta biochimica et biophysica Sinica Medium 25662616
2016 CaMKIIα C-terminal tail binds MUPP1 PDZ11 with moderate affinity (Kd = 0.47 µM) and PDZ5 with lower affinity (Kd = 25.2 µM); rationally designed peptide mutants can achieve ~10-fold improved affinity for PDZ11, establishing structure-activity relationships for CaMKIIα-MUPP1 interaction. Fluorescence titration, computational structure-based modeling, mutagenesis of peptide ligands Amino acids Medium 26984442
2017 Global or conditional (Nestin-positive cell) deletion of Mpdz in mice causes supratentorial hydrocephalus due to progressive loss of ependymal cell barrier integrity (without morphological defects in cilia or tight junctions), accompanied by diminished Pals1 expression and increased RhoA activity in astrocytes, followed by reactive astrogliosis and aqueductal stenosis. Conditional knockout mouse, MRI, immunofluorescence, in vitro barrier integrity assay, RhoA activity assay EMBO molecular medicine High 28500065
2018 MPDZ physically interacts with the intracellular C-terminus of DLL1 and DLL4 Notch ligands and enables their interaction with the adherens junction protein Nectin-2; inactivation of MPDZ impairs Notch signaling and increases blood vessel sprouting in endothelial cells and embryonic mouse hindbrain. Co-immunoprecipitation, MPDZ gene inactivation in cell models and conditional endothelial KO mice, vessel sprouting assay, Notch signaling assay eLife High 29620522
2019 In Mpdz loss-of-function mice, the permeability of the choroid plexus epithelial monolayer is abnormally high; MRI shows contrast medium penetrates brain ventricles of KO but not normal mice, and CSF protein concentration is up to 53-fold elevated, with ultrastructural evidence suggesting increased transcytosis. MRI with contrast medium, comparative proteomics of CSF, immunohistochemistry, ultrastructural analysis (electron microscopy) EMBO molecular medicine High 30518636
2019 DAPLE directly binds the PDZ3 domain of MPDZ via its C-terminal PDZ-binding motif; both co-localize at apical cell junctions. MPDZ is required for DAPLE-mediated apical constriction of neuroepithelial cells, neural plate bending, and neural tube closure in Xenopus, showing cooperative function of two NSCH-linked proteins. Co-immunoprecipitation, direct binding assay, morpholino knockdown in Xenopus, apical constriction assay in cultured cells Molecular biology of the cell High 31268831
2021 MPDZ promotes tumor suppressor activity through the Hippo-YAP pathway: MPDZ activates YAP phosphorylation at Ser127 and inhibits YAP expression by stabilizing MST1 and physically interacting with LATS1. Co-immunoprecipitation, Western blot for pathway components, MPDZ knockout and overexpression in cell lines and mice Oncogene Medium 34108620
2023 Loss of MPDZ (with PATJ) in mouse preimplantation embryos disrupts apical domain establishment, tight junctions, and actin filaments, leading to ectopic Hippo signaling activation in outer cells and suppression of Cdx2 expression and trophectoderm differentiation. Zygote microinjection of siRNA, immunofluorescence, blastocyst morphology assessment Reproduction Medium 37318097

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Multi-PDZ domain protein 1 (MUPP1) is concentrated at tight junctions through its possible interaction with claudin-1 and junctional adhesion molecule. The Journal of biological chemistry 283 11689568
2004 SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation. Neuron 237 15312654
2000 Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins. Journal of virology 213 11000240
1998 Cloning and characterization of MUPP1, a novel PDZ domain protein. FEBS letters 149 9537516
2001 Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1. The Journal of biological chemistry 120 11150294
2004 The coxsackievirus and adenovirus receptor interacts with the multi-PDZ domain protein-1 (MUPP-1) within the tight junction. The Journal of biological chemistry 107 15364909
2002 Evidence that the tandem-pleckstrin-homology-domain-containing protein TAPP1 interacts with Ptd(3,4)P2 and the multi-PDZ-domain-containing protein MUPP1 in vivo. The Biochemical journal 104 11802782
2004 Mpdz is a quantitative trait gene for drug withdrawal seizures. Nature neuroscience 96 15208631
2002 Congenic mapping of alcohol and pentobarbital withdrawal liability loci to a <1 centimorgan interval of murine chromosome 4: identification of Mpdz as a candidate gene. The Journal of neuroscience : the official journal of the Society for Neuroscience 91 11978849
2000 The multi-PDZ domain protein MUPP1 is a cytoplasmic ligand for the membrane-spanning proteoglycan NG2. Journal of cellular biochemistry 84 10967549
2007 Molecular characterization of angiomotin/JEAP family proteins: interaction with MUPP1/Patj and their endogenous properties. Genes to cells : devoted to molecular & cellular mechanisms 81 17397395
2003 Claudin-8 interacts with multi-PDZ domain protein 1 (MUPP1) and reduces paracellular conductance in epithelial cells. Cellular and molecular biology (Noisy-le-Grand, France) 74 12839333
2006 GABAB receptor association with the PDZ scaffold Mupp1 alters receptor stability and function. The Journal of biological chemistry 73 17145756
2013 Mutation in MPDZ causes severe congenital hydrocephalus. Journal of medical genetics 72 23240096
2009 Similar and distinct properties of MUPP1 and Patj, two homologous PDZ domain-containing tight-junction proteins. Molecular and cellular biology 64 19255144
2008 The PDZ protein mupp1 promotes Gi coupling and signaling of the Mt1 melatonin receptor. The Journal of biological chemistry 64 18378672
2017 Loss of Mpdz impairs ependymal cell integrity leading to perinatal-onset hydrocephalus in mice. EMBO molecular medicine 57 28500065
2008 Ablation of Cx47 in transgenic mice leads to the loss of MUPP1, ZONAB and multiple connexins at oligodendrocyte-astrocyte gap junctions. The European journal of neuroscience 46 18973575
2000 The direct association of the multiple PDZ domain containing proteins (MUPP-1) with the human c-Kit C-terminus is regulated by tyrosine kinase activity. FEBS letters 44 11018522
2008 Hypertonic stress increases claudin-4 expression and tight junction integrity in association with MUPP1 in IMCD3 cells. Proceedings of the National Academy of Sciences of the United States of America 43 18840681
2007 The tight junction protein, MUPP1, is up-regulated by hypertonicity and is important in the osmotic stress response in kidney cells. Proceedings of the National Academy of Sciences of the United States of America 41 17690246
2011 The effector and scaffolding proteins AF6 and MUPP1 interact with connexin36 and localize at gap junctions that form electrical synapses in rodent brain. The European journal of neuroscience 40 22211808
2019 Murine MPDZ-linked hydrocephalus is caused by hyperpermeability of the choroid plexus. EMBO molecular medicine 38 30518636
2018 MPDZ promotes DLL4-induced Notch signaling during angiogenesis. eLife 34 29620522
2017 Hydrocephalus due to multiple ependymal malformations is caused by mutations in the MPDZ gene. Acta neuropathologica communications 34 28460636
2009 CaMKIIalpha interacts with multi-PDZ domain protein MUPP1 in spermatozoa and prevents spontaneous acrosomal exocytosis. Journal of cell science 34 19934217
2008 The Multi-PDZ domain protein MUPP1 as a lipid raft-associated scaffolding protein controlling the acrosome reaction in mammalian spermatozoa. Journal of cellular physiology 33 17894389
2008 The neuronal RhoA GEF, Tech, interacts with the synaptic multi-PDZ-domain-containing protein, MUPP1. Journal of neurochemistry 30 18537874
2009 Sequence variations of the human MPDZ gene and association with alcoholism in subjects with European ancestry. Alcoholism, clinical and experimental research 29 19175764
2013 The multi-PDZ domain protein-1 (MUPP-1) expression regulates cellular levels of the PALS-1/PATJ polarity complex. Experimental cell research 28 23880463
2008 Interaction of the human somatostatin receptor 3 with the multiple PDZ domain protein MUPP1 enables somatostatin to control permeability of epithelial tight junctions. FEBS letters 27 19071123
2003 Expression of MUPP1 protein in mouse brain. Brain research 27 12706259
2012 A complex of synaptic adhesion molecule CADM1, a molecule related to autism spectrum disorder, with MUPP1 in the cerebellum. Journal of neurochemistry 26 22994563
2011 Mpdz null allele in an avian model of retinal degeneration and mutations in human leber congenital amaurosis and retinitis pigmentosa. Investigative ophthalmology & visual science 25 21862650
2021 MPDZ as a novel epigenetic silenced tumor suppressor inhibits growth and progression of lung cancer through the Hippo-YAP pathway. Oncogene 22 34108620
2019 DAPLE and MPDZ bind to each other and cooperate to promote apical cell constriction. Molecular biology of the cell 21 31268831
2015 CASPR2 forms a complex with GPR37 via MUPP1 but not with GPR37(R558Q), an autism spectrum disorder-related mutation. Journal of neurochemistry 20 25977097
2016 The multiple PDZ domain protein Mpdz/MUPP1 regulates opioid tolerance and opioid-induced hyperalgesia. BMC genomics 18 27129385
2013 Novel MPDZ/MUPP1 transgenic and knockdown models confirm Mpdz's role in ethanol withdrawal and support its role in voluntary ethanol consumption. Addiction biology 18 24118405
2006 The multi PDZ domain protein MUPP1 as a putative scaffolding protein for organizing signaling complexes in the acrosome of mammalian spermatozoa. Journal of andrology 18 16452527
2004 Potential pleiotropic effects of Mpdz on vulnerability to seizures. Genes, brain, and behavior 16 14960011
1999 Identification, sequence, and mapping of the mouse multiple PDZ domain protein gene, Mpdz. Genomics 16 10395806
2019 Observation of nine previously reported and 10 non-reported SLC4A11 mutations among 20 Iranian CHED probands and identification of an MPDZ mutation as possible cause of CHED and FECD in one family. The British journal of ophthalmology 15 31420327
2007 Design, synthesis, and evaluation of linear and cyclic peptide ligands for PDZ10 of the multi-PDZ domain protein MUPP1. Biochemistry 15 17939682
2018 Compound heterozygous variants in the multiple PDZ domain protein (MPDZ) cause a case of mild non-progressive communicating hydrocephalus. BMC medical genetics 14 29499638
2014 The scaffold protein MUPP1 regulates odorant-mediated signaling in olfactory sensory neurons. Journal of cell science 14 24652834
2021 ADAMTS1, MPDZ, MVD, and SEZ6: candidate genes for autosomal recessive nonsyndromic hearing impairment. European journal of human genetics : EJHG 12 34135477
2018 Analysis of multiple genetic loci reveals MPDZ-NF1B rs1324183 as a putative genetic marker for keratoconus. The British journal of ophthalmology 11 30002070
2014 Using a collection of MUPP1 domains to investigate the similarities of neurotransmitter transporters C-terminal PDZ motifs. Biochemical and biophysical research communications 10 25305483
2010 Visualization and analysis of a cardio vascular disease- and MUPP1-related biological network combining text mining and data warehouse approaches. Journal of integrative bioinformatics 10 21068463
2016 Structure-based identification of CaMKIIα-interacting MUPP1 PDZ domains and rational design of peptide ligands to target such interaction in human fertilization. Amino acids 9 26984442
2014 Mpdz expression in the caudolateral substantia nigra pars reticulata is crucially involved in alcohol withdrawal. Genes, brain, and behavior 9 25109596
2022 Genomic analysis of paired IDHwt glioblastomas reveals recurrent alterations of MPDZ at relapse after radiotherapy and chemotherapy. Journal of the neurological sciences 8 35259554
2009 MUPP1 complexes renal K+ channels to alter cell surface expression and whole cell currents. American journal of physiology. Renal physiology 8 19420109
2022 Novel Compound Heterozygous Variations in MPDZ Gene Caused Isolated Bilateral Macular Coloboma in a Chinese Family. Cells 6 36429029
2008 The MUPP1-SynGAPalpha protein complex does not mediate activity-induced LTP. Molecular and cellular neurosciences 6 18417361
2014 Neuronal cell-surface protein neurexin 1 interaction with multi-PDZ domain protein MUPP1. Bioscience, biotechnology, and biochemistry 5 25036961
2012 Profiling retinal biochemistry in the MPDZ mutant retinal dysplasia and degeneration chick: a model of human RP and LCA. Investigative ophthalmology & visual science 5 22159006
2024 Prenatal phenotype of a homozygous nonsense MPDZ variant in a fetus with severe congenital hydrocephalus. Prenatal diagnosis 4 38498110
2024 Expanding the spectrum of phenotypes for MPDZ: Report of four unrelated families and review of the literature. Clinical genetics 3 38857973
2023 Retinal manifestations in autosomal recessive MPDZ maculopathy: report of two cases and literature review. Ophthalmic genetics 3 36594712
2020 Comparison of SynCAM1/CADM1 PDZ interactions with MUPP1 using mammalian and bacterial pull-down systems. Brain and behavior 3 32108449
2023 PATJ and MPDZ are required for trophectoderm lineage specification in early mouse embryos. Reproduction (Cambridge, England) 2 37318097
2017 Rational design of an orthogonal noncovalent interaction system at the MUPP1 PDZ11 complex interface with CaMKIIα-derived peptides in human fertilization. Molecular bioSystems 2 28832060
2015 Biochemical and structural characterization of MUPP1-PDZ4 domain from Mus musculus. Acta biochimica et biophysica Sinica 2 25662616
2024 Expanding the phenotypic spectrum of MPDZ gene variants: A case report with prenatally detected Dandy-Walker malformation and single ventricle heart. Prenatal diagnosis 1 38818866
2022 Evaluating the association between MPDZ-NF1B rs1324183 and keratoconus in an independent northwestern Chinese population. BMC ophthalmology 1 35305607