Affinage

Showing MPDZ — MUPP1 is a alias.

MPDZ

Multiple PDZ domain protein · UniProt O75970

Length
2070 aa
Mass
221.6 kDa
Annotated
2026-06-10
68 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MPDZ/MUPP1 is a large, catalytically inert cytoplasmic scaffold built from 13 PDZ domains that serves as a multivalent organizing platform at epithelial tight junctions, cell-cell junctions, and neuronal synapses, clustering transmembrane and signaling partners through their C-terminal PDZ-binding motifs (PMID:9537516, PMID:11689568). At tight junctions it directly binds claudins (claudin-1 via PDZ10, claudin-8 via PDZ9), JAM (PDZ9), and CAR (PDZ13), and is recruited to cell-cell contacts by these partners to maintain the paracellular barrier; overexpression increases transepithelial resistance and its loss reduces it (PMID:11689568, PMID:12839333, PMID:15364909). Under hypertonic stress MPDZ is upregulated and required for barrier integrity by correctly localizing claudin-4 and preventing its lysosomal degradation (PMID:17690246, PMID:18840681). In vivo, Mpdz knockout in mice causes congenital hydrocephalus through progressive ependymal and choroid plexus barrier failure, reduced Pals1, elevated RhoA activity, and greatly increased choroid plexus transcytosis (PMID:28500065, PMID:30518636). The scaffold serves multiple GPCRs and channels: it stabilizes GABA(B)R2 and prolongs its signaling, anchors the MT1 melatonin receptor to support Gi coupling, targets somatostatin receptor 3 to junctions, and traffics GPR37 to the cell surface (PMID:17145756, PMID:18378672, PMID:19071123, PMID:25977097). At synapses MPDZ assembles a SynGAP-CaMKII complex whose Ca2+/calmodulin-triggered dissociation drives SynGAP dephosphorylation and AMPA receptor potentiation, and it organizes an analogous CaMKIIα platform at the sperm acrosome that gates acrosomal exocytosis (PMID:15312654, PMID:19934217, PMID:18417361). MPDZ also acts in developmental signaling, promoting DLL1/DLL4-Notch signaling by anchoring the ligands to adherens junctions via Nectin-2 to restrain vessel sprouting (PMID:29620522), cooperating with DAPLE in apical constriction during neural plate bending (PMID:31268831), and activating the Hippo pathway by stabilizing MST1 and binding LATS1 to suppress YAP and limit proliferation, migration, and metastasis (PMID:34108620).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 Medium

    Established MPDZ as a non-catalytic, 13-PDZ-domain protein, framing it as a scaffold rather than an enzyme and giving it its first binding partner.

    Evidence Yeast two-hybrid against the 5-HT2C receptor C-terminus

    PMID:9537516

    Open questions at the time
    • No localization or functional role demonstrated
    • Physiological relevance of 5-HT2C binding not tested in vivo
  2. 2000 Medium

    Showed the PDZ array is a promiscuous docking surface for diverse C-terminal motifs, including a receptor tyrosine kinase and a proteoglycan, defining MUPP1 as a multivalent adaptor and revealing that viral oncoproteins hijack it.

    Evidence Y2H, GST pull-down, Co-IP for NG2, c-Kit, and adenovirus/HPV oncoprotein binding with loss-of-function mutants

    PMID:10967549 PMID:11000240 PMID:11018522

    Open questions at the time
    • Endogenous consequences of NG2 and c-Kit binding unresolved
    • Whether oncoprotein-driven MUPP1 degradation explains transformation not established
  3. 2001 High

    Localized MUPP1 to tight junctions and mapped domain-specific binding to claudin-1, JAM, and the 5-HT2C receptor, establishing it as an organizing scaffold of the junctional cytoplasmic plaque.

    Evidence Y2H, in vitro binding, domain-mapping mutagenesis, immunoEM, and reciprocal Co-IP from choroid plexus

    PMID:11150294 PMID:11689568

    Open questions at the time
    • Functional contribution to barrier not yet measured
    • Stoichiometry of multi-partner assembly unknown
  4. 2003 High

    Demonstrated MUPP1 directly modulates barrier function, moving it from a structural component to a functional regulator of paracellular permeability.

    Evidence Claudin-8 binding via PDZ9 with TER and FITC-dextran flux assays in MDCK cells

    PMID:12839333

    Open questions at the time
    • Mechanism linking claudin clustering to conductance not detailed
    • In vivo relevance untested in this study
  5. 2004 High

    Defined the synaptic role: MUPP1 holds SynGAP and CaMKII together, and Ca2+-triggered complex dissociation transduces NMDAR signaling into AMPAR potentiation.

    Evidence Co-IP, peptide-mediated disruption, AMPAR electrophysiology, and siRNA in hippocampal neurons; CAR-dependent TJ recruitment shown separately

    PMID:15312654 PMID:15364909

    Open questions at the time
    • Direct kinase/phosphatase identities acting on SynGAP within complex incomplete
    • Behavioral consequences not addressed
  6. 2007 Medium

    Quantified the PDZ10 binding hierarchy and identified phosphorylation as a switch, and showed MUPP1 is stress-induced to sustain barrier function.

    Evidence ITC of PDZ10 with multiple peptides; antibody-array proteomics and siRNA-TER under hypertonic stress in collecting duct cells

    PMID:17690246 PMID:17939682

    Open questions at the time
    • Whether the phospho-switch operates on endogenous partners in cells untested
    • Upstream kinases inducing MUPP1 under hypertonicity unidentified
  7. 2008 High

    Generalized MUPP1 as a GPCR/channel stabilizer and trafficker, and uncovered roles at gap junctions, the acrosome, and a neuronal RhoA-GEF, broadening it beyond tight junctions.

    Evidence Co-IP/ITC for GABA(B)R2, MT1, hSSTR3, Kir4.2, Cx47/Cx32, Tech; inhibitory antibody and CaMKIIα displacement in sperm; SynGAP peptide electrophysiology

    PMID:17145756 PMID:17894389 PMID:18378672 PMID:18417361 PMID:18537874 PMID:18973575 PMID:19071123 PMID:19934217

    Open questions at the time
    • Tissue-specific selectivity among competing PDZ partners unresolved
    • Whether one MUPP1 molecule integrates these complexes simultaneously unknown
  8. 2009 High

    Distinguished MUPP1 from its paralog Patj, showing MUPP1 is dispensable for polarity establishment but modulates Kir4.2 surface expression, refining its non-redundant niche.

    Evidence Comparative Co-IP and siRNA-TER for Patj; reciprocal Co-IP and oocyte electrophysiology for Kir4.2

    PMID:19255144 PMID:19420109

    Open questions at the time
    • Molecular basis of MUPP1/Patj functional divergence incompletely defined
    • Renal physiology of Kir4.2 regulation not tested in vivo
  9. 2015 Medium

    Provided the first atomic view of a MUPP1 PDZ fold and high-resolution binding affinities, rationalizing ligand selectivity and CaMKIIα docking to PDZ11.

    Evidence 1.6 Å crystal structure of PDZ4; fluorescence titration of CaMKIIα to PDZ11/PDZ5; GPR37 trafficking and disease-mutant comparison

    PMID:25662616 PMID:25977097 PMID:26984442

    Open questions at the time
    • No multi-domain or full-length structure
    • Binding-pocket mutagenesis of PDZ4 not performed
  10. 2017 High

    Established MPDZ as a hydrocephalus gene in vivo, linking barrier failure, reduced Pals1, and elevated RhoA to ependymal and choroid plexus pathology with increased transcytosis.

    Evidence Global and conditional knockout mice with MRI, TER, RhoA assays, CSF proteomics, and ultrastructure

    PMID:28500065 PMID:30518636

    Open questions at the time
    • Direct molecular link between MPDZ loss and RhoA elevation unresolved
    • Why TJ morphology is normal yet barrier fails not fully explained
  11. 2019 High

    Connected MPDZ to developmental signaling, showing it anchors Notch ligands via Nectin-2 to restrain angiogenesis and cooperates with DAPLE to drive apical constriction in neurulation.

    Evidence Co-IP, endothelial-specific KO with hindbrain/tumor angiogenesis; DAPLE PDZ3 mapping with Xenopus morpholino constriction assays

    PMID:29620522 PMID:31268831

    Open questions at the time
    • How junctional anchoring mechanistically activates Notch signaling unresolved
    • Relationship between angiogenic and neurulation roles untested
  12. 2021 Medium

    Placed MPDZ in the Hippo pathway as a tumor suppressor that stabilizes MST1 and engages LATS1 to phosphorylate and suppress YAP, and showed it is required for trophectoderm specification.

    Evidence Co-IP, MST1 stabilization, p-YAP Western, KO mouse metastasis model; combined PATJ/MPDZ RNAi in mouse embryos with Hippo/Cdx2 readouts

    PMID:34108620 PMID:37318097

    Open questions at the time
    • Direct vs indirect MST1 stabilization mechanism unclear
    • Single-lab Hippo data not independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single 13-PDZ scaffold dynamically selects among its many competing partners across tissues, and how its junctional architecture is mechanistically coupled to RhoA, Notch, and Hippo signaling outputs, remains unresolved.
  • No full-length or multi-domain structure to model combinatorial occupancy
  • Mechanistic link from scaffolding to RhoA/Hippo regulation undefined
  • Stoichiometry and tissue-specific partner prioritization unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 4 GO:0005198 structural molecule activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-1500931 Cell-Cell communication 4 R-HSA-162582 Signal Transduction 4 R-HSA-112316 Neuronal System 3 R-HSA-1266738 Developmental Biology 3
Partners
CLDN4CXADRDLL4GABBR2JAMLATS1MTNR1ASYNGAP1
Complex memberships
SynGAP-CaMKII synaptic complextight junction

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 MUPP1 (MPDZ) was identified as a novel protein containing 13 PDZ domains that interacts with the C-terminal domain of the 5-HT2C receptor, identified via yeast two-hybrid screen. No obvious catalytic domain was found, suggesting a scaffolding role. Yeast two-hybrid screening FEBS letters Medium 9537516
2001 MUPP1 is concentrated at tight junctions in polarized epithelial cells through direct binding to claudin-1 (via PDZ10) and junctional adhesion molecule (JAM, via PDZ9), establishing MUPP1 as a multivalent scaffold at tight junctions. Yeast two-hybrid, in vitro binding assays with recombinant MUPP1, immunofluorescence confocal microscopy, immunoelectron microscopy, transfection experiments The Journal of biological chemistry High 11689568
2001 The C-terminus of the 5-HT2C receptor (SSV/SXV motif) selectively interacts with PDZ10 of MUPP1; this interaction was confirmed by co-immunoprecipitation from transfected COS-7 cells and from rat choroid plexus; co-clustering of the two proteins was SXV motif-dependent; interaction triggered a conformational change in MUPP1. 5-HT2A and 5-HT2B also bind MUPP1 PDZ domains in vitro. Yeast two-hybrid, site-directed mutagenesis of receptor C-terminus, co-immunoprecipitation, immunocytochemistry, in vitro binding The Journal of biological chemistry High 11150294
2000 MUPP1 interacts with the cytoplasmic domain of the NG2 chondroitin sulfate proteoglycan through an N-terminal PDZ domain region; the NG2 C-terminus is required for the interaction. Co-immunoprecipitation confirmed the interaction in situ in cells expressing both molecules. Yeast two-hybrid, GST pull-down assay, co-immunoprecipitation Journal of cellular biochemistry Medium 10967549
2000 The PDZ-binding motifs of adenovirus E4-ORF1 and HPV-18 E6 oncoproteins mediate binding to MUPP1; E4-ORF1 aberrantly sequesters MUPP1 in the cytoplasm, while HPV-18 E6 targets MUPP1 for degradation. Mutant viral proteins unable to bind MUPP1 lack these activities. Co-immunoprecipitation, subcellular localization assays, mutant viral protein analysis, cell-based degradation assays Journal of virology High 11000240
2002 TAPP1 and TAPP2 interact with the 10th and 13th PDZ domains of MUPP1 through their C-terminal amino acids; endogenous TAPP1 co-immunoprecipitates endogenous MUPP1 from 293 cells, suggesting physiological interaction. PtdIns(3,4)P2-driven plasma membrane translocation of TAPP1 could thereby recruit MUPP1. Co-immunoprecipitation of endogenous proteins, yeast two-hybrid, domain mapping The Biochemical journal Medium 11802782
2003 Claudin-8 interacts with MUPP1 through PDZ9; both co-localize and co-immunoprecipitate at tight junctions in MDCK cells. Over-expression of MUPP1 reduces epithelial paracellular conductance (increased TER), indicating a functional role in tight junction barrier function. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence, transepithelial electrical resistance measurement, FITC-dextran paracellular flux assay Cellular and molecular biology High 12839333
2004 MUPP1 forms a synaptic complex with SynGAP and CaMKII in hippocampal neurons; SynGAP and CaMKII are brought together through direct physical interaction with PDZ domains of MUPP1. In this complex, SynGAP is phosphorylated. Ca2+/CaM binding to CaMKII dissociates it from the MUPP1 complex, leading to SynGAP dephosphorylation, p38 MAPK inactivation, AMPAR synaptic potentiation, and increased AMPAR clusters. Co-immunoprecipitation, peptide-mediated complex disruption, AMPA receptor electrophysiology, immunofluorescence, siRNA knockdown Neuron High 15312654
2004 CAR (coxsackievirus and adenovirus receptor) interacts with MUPP1 PDZ domain 13 via its PDZ-binding motif; both co-localize and co-precipitate at tight junctions; CAR recruits MUPP1 to cell-cell contacts. siRNA knockdown of CAR inhibits MUPP1 localization to the tight junction. Yeast two-hybrid, co-immunoprecipitation from epithelial cells, in vitro binding, immunofluorescence, siRNA knockdown The Journal of biological chemistry High 15364909
2000 Human c-Kit binds specifically to the 10th PDZ domain of MUPP1 via its C-terminal sequence; a kinase-negative c-Kit mutant interacted more strongly with MUPP1 than wild-type, while constitutively activated D816V-Kit did not bind MUPP1. Deletion of V967 abolished binding and reduced kinase activity, suggesting the C-terminal tail structure influences enzymatic activity. Yeast two-hybrid, co-immunoprecipitation, domain mapping, kinase mutant analysis FEBS letters Medium 11018522
2006 GABA(B)R2 interacts with MUPP1 PDZ13; disruption of GABA(B)R2 PDZ interactions (by point mutation or siRNA knockdown of endogenous MUPP1) dramatically decreased receptor stability and attenuated the duration of GABA(B) receptor signaling, establishing MUPP1 as a regulator of GABA(B) receptor stability and signaling. PDZ domain array screen, co-immunoprecipitation, siRNA knockdown, receptor stability assay, signaling duration measurement 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 specific PDZ domains (PDZ2 and -3 for Amot and MASCOT; PDZ3 for JEAP). However, PDZ-binding motifs of Amot/JEAP proteins are not required for their localization to tight junctions, and dominant negative MUPP1 did not affect their localization. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence microscopy, biochemical fractionation, dominant negative constructs Genes to cells Medium 17397395
2008 MUPP1 binds to the G protein-coupled MT1 melatonin receptor via PDZ10 and the DSV motif at the MT1 C-terminus with high affinity (Kd ~4 nM); this interaction is independent of MT1 activation but is required for stabilizing MT1-Gi coupling and Gi-mediated signaling. Disruption of the interaction has no effect on MT1 subcellular localization, trafficking, or degradation. Co-immunoprecipitation, isothermal titration calorimetry, peptide disruption, cAMP signaling assays, immunofluorescence The Journal of biological chemistry High 18378672
2008 MUPP1 interacts with human somatostatin receptor 3 (hSSTR3) via MUPP1 PDZ domains; through this interaction, MUPP1 targets hSSTR3 to tight junctions. The interaction enables hSSTR3 to regulate transepithelial permeability in a pertussis toxin-sensitive (Gi-dependent) manner. Co-immunoprecipitation, immunofluorescence/colocalization, transepithelial permeability assay, pertussis toxin inhibition FEBS letters Medium 19071123
2008 MUPP1 is localized in lipid raft-associated membrane domains (Triton X-100-insoluble fraction) in the periacrosomal region of spermatozoa. Inhibitory antibodies against MUPP1 loaded into permeabilized sperm showed that MUPP1 controls the initial tethering and docking of the acrosomal vesicle during acrosomal exocytosis, distinct from syntaxin 2 which controls the final fusion step. Immunogold electron microscopy, detergent-resistant membrane fractionation, inhibitory antibody microinjection, controlled Ca2+ release assay Journal of cellular physiology Medium 17894389
2008 MUPP1 localizes at oligodendrocyte-astrocyte (O/A) gap junctions in brain, co-localizing with Cx32/Cx47 and Cx30/Cx43. In Cx47-knockout mice, MUPP1 (and ZONAB) labeling was absent on oligodendrocytes, while MUPP1 persisted in Cx32-knockout mice, demonstrating Cx47-dependent localization of MUPP1 at O/A gap junctions. Immunofluorescence microscopy in Cx47 and Cx32 knockout mice, co-localization analysis The European journal of neuroscience Medium 18973575
2008 CaMKIIα co-localizes with MUPP1 in the acrosomal region of spermatozoa and selectively binds to PDZ domains 10–11 of MUPP1. Ca2+/calmodulin releases CaMKIIα from the MUPP1 complex. Competitive displacement of CaMKIIα from PDZ10-11, or CaMKII kinase inhibition, significantly increases spontaneous acrosomal exocytosis, establishing MUPP1 as a platform regulating CaMKIIα-dependent acrosomal secretion. Co-immunoprecipitation, competitive peptide displacement, CaMKII inhibitor treatment, acrosomal exocytosis assay Journal of cell science High 19934217
2009 MUPP1 and Patj share binding partners (JAM1, ZO-3, Pals1, Par6, nectins) and similar localization mechanisms at tight junctions. However, functional studies show Patj is indispensable for TJ establishment and epithelial polarization, whereas MUPP1 is not. Pals1 has higher affinity for Patj than MUPP1, and Pals1-mediated Par6-aPKC activation is key for Patj function. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, transepithelial resistance measurement Molecular and cellular biology High 19255144
2009 MUPP1 complexes with the renal inwardly rectifying K+ channel Kir4.2 via its PDZ-binding motif (specifically requiring the 4 C-terminal amino acids); co-expression of MUPP1 reduces Kir4.2 cell surface expression (biotinylation assay) and whole-cell K+ currents in Xenopus oocytes. Yeast two-hybrid, reciprocal co-immunoprecipitation from rat kidney cortex and HEK-293 cells, cell surface biotinylation, Xenopus oocyte electrophysiology, immunofluorescence American journal of physiology. Renal physiology High 19420109
2011 MUPP1 associates with connexin36 (Cx36) at neuronal gap junctions via the C-terminal PDZ interaction motif of Cx36 and the 10th PDZ domain of MUPP1. Co-immunoprecipitation and pull-down assays confirmed this association in rodent brain. Co-immunoprecipitation, pull-down assays, immunofluorescence co-localization in brain sections The European journal of neuroscience Medium 22211808
2007 MUPP1 is up-regulated ~7-fold by hypertonic stress in renal inner medullary collecting duct cells; siRNA silencing of MUPP1 results in a 24% reduction in transepithelial resistance, indicating MUPP1 is required for maintenance of tight epithelial barrier properties under hypertonic conditions. Antibody array proteomics, Western blot, quantitative PCR, siRNA knockdown, transepithelial resistance measurement Proceedings of the National Academy of Sciences of the United States of America Medium 17690246
2008 Under hypertonic stress, MUPP1 interacts with claudin-4 (but not other claudins) at tight junctions; MUPP1 silencing causes claudin-4 to be mistargeted to lysosomes and degraded, reducing its expression. Silencing of claudin-4 reduces transepithelial resistance to the same degree as MUPP1 silencing, establishing that MUPP1 maintains barrier function by correctly localizing claudin-4. Co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown, transepithelial resistance measurement, lysosome inhibition rescue Proceedings of the National Academy of Sciences of the United States of America High 18840681
2008 The neuronal RhoA GEF Tech interacts with MUPP1 via PDZ domains 10 and/or 13 (both must be mutated to disrupt binding); endogenous Tech co-precipitates with MUPP1 (but not PSD-95) from hippocampal/cortical extracts. Tech and MUPP1 co-localize near synapses in cortical neurons. Yeast two-hybrid, co-transfection co-immunoprecipitation, endogenous co-immunoprecipitation from brain, PDZ domain mutagenesis, immunostaining Journal of neurochemistry Medium 18537874
2012 CADM1 (SynCAM1) C-terminal peptide associates with MUPP1 at PDZ1–5; the CADM1-MUPP1 complex further interacts with GABA(B)R2 at PDZ13. In Cadm1 KO mice, GABBR2 protein (but not mRNA) increased in cerebellum, suggesting the MUPP1-GABBR2 complex is stabilized in the absence of CADM1. Co-immunoprecipitation, domain mapping, immunofluorescence, Western blot and qPCR in knockout mice Journal of neurochemistry Medium 22994563
2013 MUPP1 depletion increases PATJ protein levels (but not mRNA), and the increased PATJ localizes at the migrating front of MCF10A cells, recruiting more PAR3. MUPP1 thus inversely regulates PATJ levels by modulating PATJ/PALS-1 complex stabilization, revealing a balance between MUPP1 and PATJ in epithelial cells. siRNA knockdown, Western blot, co-immunoprecipitation, immunofluorescence Experimental cell research Medium 23880463
2014 MUPP1 organizes a macromolecular signaling complex in mouse olfactory sensory neurons (co-immunoprecipitation). Disruption of this PDZ complex with an inhibitory peptide strongly impaired odor-evoked responses and altered activation kinetics, and also impaired response termination. Co-immunoprecipitation, inhibitory peptide disruption, electrophysiology/odor response assay Journal of cell science Medium 24652834
2015 CASPR2 and GPR37 interact with MUPP1 at PDZ3 and PDZ11 respectively; MUPP1 is required for GPR37 transport to the cell surface — GPR37 (but not the ASD-related R558Q mutant lacking effective PDZ interaction) is transported to the cell surface and to synapses by MUPP1. The R558Q mutant accumulates in the ER. Co-immunoprecipitation, domain mapping, cell surface expression assay, immunofluorescence in primary hippocampal neurons Journal of neurochemistry Medium 25977097
2017 Mpdz global or conditional (Nestin-positive cell) knockout in mice causes supratentorial hydrocephalus from postnatal day 3. Mpdz loss in cultured epithelial cells impairs barrier integrity; in astrocytes, Mpdz loss increases RhoA activity. In Mpdz-null mice, ependymal cells have normal TJ morphology but show reduced Pals1 expression and progressive loss of barrier integrity, followed by ependymal denudation and aqueductal stenosis. Conditional and global knockout mice, MRI, transepithelial resistance, RhoA activity assay, immunofluorescence, histology EMBO molecular medicine High 28500065
2018 MPDZ physically interacts with the intracellular C-terminus of Notch ligands DLL1 and DLL4 and enables their interaction with the adherens junction protein Nectin-2. MPDZ inactivation leads to impaired Notch signaling and increased blood vessel sprouting in vitro and in the embryonic mouse hindbrain. Endothelial-specific MPDZ knockout enhances tumor angiogenesis with excessive branching and poor function. Co-immunoprecipitation, genetic knockout (global and endothelial-specific conditional), in vitro Notch signaling reporter assay, mouse hindbrain angiogenesis model, tumor angiogenesis model eLife High 29620522
2019 Mpdz loss-of-function in mice causes abnormally high permeability of the choroid plexus epithelium; contrast MRI showed penetration into brain ventricles, and CSF proteomic analysis showed up to 53-fold increased protein concentration, indicating substantially increased transcytosis through the choroid plexus epithelial cells. Magnetic resonance imaging with contrast, comparative CSF proteomics, ultrastructural analysis, immunohistochemistry EMBO molecular medicine High 30518636
2019 DAPLE directly binds to PDZ3 of MPDZ via its PDZ-binding motif; both co-localize at apical junctions of neuroepithelial cells. MPDZ is required for apical constriction of neuroepithelial cells and neural plate bending in Xenopus. MPDZ depletion blunts DAPLE-mediated apical constriction in cultured cells, establishing cooperative function between the two proteins at apical junctions. Co-immunoprecipitation, domain mapping, Xenopus morpholino knockdown, cell constriction assay, immunofluorescence Molecular biology of the cell High 31268831
2021 MPDZ activates the Hippo pathway by stabilizing MST1 and interacting with LATS1, resulting in phosphorylation of YAP (Ser127) and inhibition of YAP expression. MPDZ knockdown promotes cell proliferation, migration, and invasion in vitro and in vivo, and MPDZ-knockout mice show increased tumor metastasis. Co-immunoprecipitation (MPDZ with LATS1, stabilization of MST1), overexpression and siRNA knockdown, Western blot for p-YAP, in vitro cell assays, in vivo mouse tumor model Oncogene Medium 34108620
2008 Disruption of the MUPP1–SynGAPα interaction in CA1 hippocampal neurons (using peptides from mutual binding sites) enhanced excitatory postsynaptic currents (EPSCs) but this potentiation did NOT occlude pairing-induced LTP, indicating the MUPP1-SynGAPα complex dissociation triggers AMPAR enhancement by a mechanism distinct from activity-induced LTP. Intracellular peptide perfusion in hippocampal slices, whole-cell patch-clamp electrophysiology, LTP induction Molecular and cellular neurosciences Medium 18417361
2015 Crystal structure of MUPP1-PDZ4 domain (Mus musculus) resolved at 1.6 Å; the structure contains three α-helices and six β-strands in a canonical PDZ fold; GLGI motif, L562/A564, and H605/V608/L612 form the PDZ binding pocket that accommodates C-terminal ligands. X-ray crystallography, size-exclusion chromatography, thermal denaturation Acta biochimica et biophysica Sinica Medium 25662616
2007 ITC measurements of PDZ10 binding to C-terminal peptides from known partners (5-HT2c, c-kit, hTapp1, mTapp2, TARP, NG2, claudin-1, HPV-18 E6) revealed c-kit and 5-HT2c peptides as strongest binders (Kd ~5.2 and ~8.5 µM). Phosphoserine at P-1 or P-2 positions decreased affinity, suggesting reversible phosphorylation as a mechanism to regulate PDZ10-mediated interactions. Isothermal titration calorimetry (ITC), synthetic peptide binding, cyclic peptide design Biochemistry Medium 17939682
2023 PATJ and MPDZ are required for trophectoderm lineage specification in early mouse embryos; combined depletion impairs blastocyst formation, breaks down apical CRB and PAR polarity complexes, disrupts tight junctions and actin filaments, and causes ectopic Hippo signaling activation (YAP phosphorylation and mislocalization) in outer cells, suppressing Cdx2 expression. RNA interference by microinjection into zygotes, immunofluorescence, Western blot, Hippo pathway readout Reproduction (Cambridge, England) Medium 37318097
2016 CaMKIIα binds to MUPP1 PDZ11 as the primary high-affinity domain (Kd ~0.47 µM by fluorescence titration) and to PDZ5 with lower affinity (Kd ~25 µM), through a class II PDZ-binding motif (SGAPSV-COOH). Structure-based peptide design yielded mutants with ~10-fold improved affinity for PDZ11, providing lead molecules to target the CaMKIIα-MUPP1 interaction in fertilization. Computational structure-based analysis, fluorescence spectroscopy titration, systematic mutagenesis of peptide residues Amino acids Medium 26984442

Source papers

Stage 0 corpus · 68 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 284 11689568
2004 SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation. Neuron 238 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 108 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 58 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
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 41 22211808
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
2019 Murine MPDZ-linked hydrocephalus is caused by hyperpermeability of the choroid plexus. EMBO molecular medicine 38 30518636
2009 CaMKIIalpha interacts with multi-PDZ domain protein MUPP1 in spermatozoa and prevents spontaneous acrosomal exocytosis. Journal of cell science 35 19934217
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
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 34 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
2012 A complex of synaptic adhesion molecule CADM1, a molecule related to autism spectrum disorder, with MUPP1 in the cerebellum. Journal of neurochemistry 28 22994563
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
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
2026 Sphingosine-1-phosphate cross-talks to Notch via a S1PR1-Dll4-MPDZ complex to regulate endothelial barrier function. bioRxiv : the preprint server for biology 0 42239339

Missed literature

Know a paper Affinage missed for MPDZ? Flag it for the maintainers and the community.

No submissions yet.