Affinage

PALS1

Protein PALS1 · UniProt Q8N3R9

Length
675 aa
Mass
77.3 kDa
Annotated
2026-06-10
51 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PALS1 (MPP5) is an evolutionarily conserved MAGUK scaffold that nucleates the apical CRB3–PALS1–PATJ polarity complex governing epithelial tight junction assembly and apicobasal polarization (PMID:11927608, PMID:12527193, PMID:14718565). Through distinct binding modules it assembles a multiprotein scaffold: its PDZ domain engages the Crumbs cytoplasmic tail, while structural work shows the PDZ–SH3–GK tandem acts as a supramodule in which all three domains cooperate to bind the Crumbs tail with ~70 nM affinity, far exceeding the isolated PDZ (PMID:11927608, PMID:25385611); a gating Phe residue in the PDZ groove regulates ligand access (PMID:25760605). Its tandem L27 domains drive supramolecular assembly, with the L27N domain heterodimerizing with PATJ and the L27C domain binding mLin-7/MALS, forming cognate, mutually independent heterodimeric pairs (PMID:11927608, PMID:15863617, PMID:22337881). PALS1 physically links the CRB and Par complexes, as the Par-6 PDZ domain recognizes an internal N-terminal sequence in PALS1 in a Cdc42-independent manner, with Par-6 and PATJ competing for binding (PMID:15475968, PMID:15140881). Loss-of-function in MDCK cells delays tight junction formation, fails to recruit aPKC, abolishes PATJ expression, and prevents lumen formation (PMID:14718565), and PALS1 additionally controls E-cadherin surface delivery via the exocyst (PMID:17182851) and junctional RhoA localization, with bicellular tight junction protein positioning requiring the PATJ interaction (PMID:38265145). In specialized tissues PALS1 maintains retinal architecture by sustaining apical Crumbs complex localization, with its loss causing photoreceptor degeneration (PMID:16885194, PMID:22114289, PMID:22398208); controls Schwann cell radial sorting and myelin extension in concert with Par3 (PMID:20237282, PMID:26203142); and maintains cerebellar and cortical progenitor pools, acting upstream of entotic cell-in-cell death and Trp53 in microcephaly pathogenesis (PMID:26657772, PMID:36604424). Beyond canonical polarity, PALS1 restrains Arf6/Rac1 activity redundantly with SMAP1 to limit colorectal cancer migration and invasion (PMID:33941200, PMID:36494580) and promotes nuclear exclusion of YAP/TAZ (PMID:39859373). PALS1 is subverted by coronavirus E proteins, whose C-terminal PDZ-binding motifs bind a pocket formed jointly by the PALS1 PDZ and SH3 domains, redistributing PALS1 and disrupting junction formation (PMID:20861307, PMID:34103506, PMID:34117354).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2002 High

    Established PALS1 as the central scaffold of a conserved apical polarity complex by mapping its distinct binding modules to discrete partners.

    Evidence Co-IP, pulldowns, and domain mapping defining L27N–PATJ, L27C–mLin-7, and PDZ–CRB1 interactions

    PMID:11927608

    Open questions at the time
    • Stoichiometry and ordered assembly of the full complex not resolved
    • No structural basis for the interactions at this stage
  2. 2003 High

    Demonstrated functionally that the CRB3–PALS1 PDZ interaction is required for tight junction formation and epithelial polarization, moving PALS1 from binding partner to functional regulator.

    Evidence Dominant-negative chimera overexpression and calcium switch / cyst morphogenesis assays in MDCK cells; CRB3 Co-IP and localization

    PMID:12527193 PMID:12771187

    Open questions at the time
    • Dominant-negative approach does not exclude off-target scaffolding effects
    • Downstream effectors not defined
  3. 2004 High

    Defined PALS1 as essential for apical polarity machinery by showing its depletion fails to recruit aPKC and abolishes PATJ, and revealed a non-canonical internal binding mode bridging CRB and Par complexes.

    Evidence Stable siRNA knockdown with TEER/cyst readouts; crystal structure of Par-6 PDZ–PALS1 internal ligand complex with mutagenesis and competition assays

    PMID:14718565 PMID:15140881 PMID:15475968

    Open questions at the time
    • Regulation of Par-6 versus PATJ competition in vivo not established
    • How aPKC recruitment is coupled mechanistically not resolved
  4. 2005 High

    Extended the PALS1 interactome to MPP4/MPP3 and ezrin and resolved the L27 tetrameric assembly principle, linking PALS1 scaffolding to retinal and apical membrane organization.

    Evidence Yeast two-hybrid, GST pulldown, Co-IP, immunoEM in retina; NMR structures of L27 heterodimer pairs; ezrin loss-of-function in parietal cells

    PMID:15558731 PMID:15677456 PMID:15863617 PMID:15914641

    Open questions at the time
    • GAT1 stabilization mechanism not defined (Medium evidence)
    • Physiological role of MPP4/MPP3 recruitment to PALS1 not fully tested in vivo
  5. 2006 High

    Showed PALS1 acts beyond tight junctions to control adherens junction E-cadherin trafficking via the exocyst and is required for Crumbs-family localization in retinal glia.

    Evidence Stable knockdown with E-cadherin surface biotinylation and exocyst localization in MDCK; RNAi with immunoEM in Müller glia

    PMID:16519681 PMID:16885194 PMID:17182851

    Open questions at the time
    • Direct link between PALS1 and exocyst recruitment not biochemically defined
    • Whether PALS1 trafficking role is separable from polarity scaffolding unclear
  6. 2009 High

    Placed nephrocystins (NPHP1/NPHP4) in the same polarity pathway as PALS1, connecting the complex to ciliogenesis and cystogenesis.

    Evidence Co-IP and shRNA knockdown phenocopying PALS1 depletion in MDCK 3D cysts with cilia analysis

    PMID:19755384

    Open questions at the time
    • Direct versus indirect nature of the nephrocystin–PALS1 interaction not fully resolved
    • Mechanism linking PALS1 to ciliary function not defined
  7. 2011 High

    Established an essential in vivo structural role for PALS1 in maintaining the retinal Crumbs complex and architecture, and reported a non-polarity role in TCR-driven NF-κB signaling.

    Evidence Conditional knockdown mouse with ERG/OCT/immunohistochemistry; siRNA knockdown with NF-κB reporter in T cells

    PMID:21479189 PMID:22114289

    Open questions at the time
    • Mechanism coupling PALS1 to NF-κB activation not defined (Medium evidence)
    • Whether retinal phenotype is purely structural or signaling-dependent not separated
  8. 2012 High

    Resolved the L27 heterotrimeric assembly mechanism and demonstrated mutual interdependence of PALS1 and Crb proteins for apical localization in a disease-relevant retinal model.

    Evidence Crystal structure of Patj/Pals1/Mals2 L27 heterotrimer; conditional Pals1 knockout mouse mimicking Leber congenital amaurosis

    PMID:22337881 PMID:22398208

    Open questions at the time
    • How L27 assembly is regulated dynamically in cells not addressed
    • Genetic causation in human retinal disease not directly tested in these studies
  9. 2014 High

    Defined the structural basis for high-affinity Crumbs recognition, showing the PDZ–SH3–GK tandem functions as an integrated supramodule whose interdomain contacts are required for polarity function.

    Evidence Crystal structure of PALS1 PDZ-SH3-GK–Crb-CT with ITC and MDCK cyst polarity assay

    PMID:25385611

    Open questions at the time
    • Whether supramodule conformation is regulated in vivo unclear
    • Allosteric communication between domains not kinetically dissected
  10. 2015 High

    Revealed regulated, gated access of Crumbs to the PDZ groove and extended PALS1 function to Schwann cell radial sorting/myelination and cerebellar progenitor maintenance via interactions with Par3 and Shh-independent control of differentiation.

    Evidence Apo/bound PDZ crystal structures with binding assays; conditional knockouts in Schwann cells, oligodendrocytes, and cerebellar progenitors with epistasis to Smo; Drosophila Stardust genetics

    PMID:25760605 PMID:25847234 PMID:26203142 PMID:26657772

    Open questions at the time
    • Physiological trigger controlling the PDZ gating residue unknown
    • Mechanism by which PALS1 prevents premature cerebellar differentiation not molecularly defined
  11. 2016 High

    Identified VE-cadherin as a direct PALS1 recruiter at endothelial junctions, linking PALS1 scaffolding to vascular lumen formation.

    Evidence Co-IP, pulldown, mutagenesis of VE-cadherin membrane-proximal motif, lumen formation assay

    PMID:27466317

    Open questions at the time
    • How VE-cadherin-bound PALS1 directs apical membrane specification not detailed
    • Relationship to Crumbs binding at the same PDZ not addressed
  12. 2017 Medium

    Demonstrated PALS1 dosage sensitivity in vivo, with haploinsufficiency causing renal cysts and dysregulated Hippo–TGF-β crosstalk.

    Evidence Conditional heterozygous Pals1 knockout mouse with histology and signaling readouts; Drosophila nephrocyte analysis

    PMID:28154200

    Open questions at the time
    • Mechanistic detail of Hippo/TGF-β crosstalk regulation limited
    • Direct molecular targets in these pathways not identified
  13. 2021 High

    Defined how coronavirus E proteins subvert PALS1, showing the viral C-terminal motif binds a pocket formed jointly by the PDZ and SH3 domains with specificity excluding MERS-CoV.

    Evidence Cryo-EM of PALS1–SARS-CoV-2 E complex; crystal structures of PDZ bound to SARS-CoV-1/2 E motifs with affinity measurements and MERS negative control; earlier infection model showing PALS1 redistribution

    PMID:20861307 PMID:34103506 PMID:34117354

    Open questions at the time
    • Functional consequence of E-PALS1 sequestration on infection outcome not fully dissected here
    • Whether endogenous ligands engage the same composite pocket not tested
  14. 2022 High

    Uncovered a Crumbs/PATJ-independent tumor-suppressive function whereby PALS1 restrains Arf6/Rac1 activity redundantly with SMAP1 to limit migration and invasion, and a role in ciliary base regulation via angiomotin and KIF13B.

    Evidence Pals1 and SMAP1 knockout with GTPase activity assays and migration assays plus patient cohort; Co-IP and live imaging of Ap80-PALS1-KIF13B at the cilium

    PMID:35673984 PMID:36494580

    Open questions at the time
    • Direct molecular mechanism by which PALS1 inhibits Arf6 GTPase not defined
    • Ciliary KIF13B recruitment role rests on single-lab Medium evidence
  15. 2023 High

    Placed PALS1 loss upstream of entotic cell-in-cell death and Trp53 in cortical microcephaly pathogenesis, linking polarity disruption to mitotic and cytokinesis defects.

    Evidence Conditional Pals1 knockout mouse with ROCK inhibition, Trp53 genetic rescue, and live imaging of division

    PMID:36604424

    Open questions at the time
    • How PALS1 loss mechanistically triggers ROCK-dependent CIC formation not defined
    • Direct molecular link from polarity loss to mitotic lengthening unclear
  16. 2024 High

    Resolved that PALS1 positions tight junction proteins specifically at bicellular contacts and controls junctional RhoA, requiring its PATJ interaction.

    Evidence CRISPR knockout in MDCKII with TEER, Ca2+/F-actin reassembly assays, and RhoA localization

    PMID:38265145

    Open questions at the time
    • Mechanism linking PALS1 to RhoA junctional retention not defined
    • How bicellular versus tricellular targeting is determined unclear
  17. 2025 Medium

    Identified PALS1 as a PDZ-dependent regulator of YAP/TAZ nuclear exclusion in liver cancer, connecting the scaffold to Hippo effector localization.

    Evidence Co-IP, PLA, and PDZ deletion analysis in HCC cells with tissue correlation

    PMID:39859373

    Open questions at the time
    • Mechanism of PALS1-mediated nuclear exclusion not defined
    • Single-lab evidence without in vivo functional validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PALS1's diverse functions—canonical polarity scaffolding versus Crumbs/PATJ-independent control of small-GTPase signaling, Hippo/YAP-TAZ, and progenitor maintenance—are integrated and differentially regulated across tissues remains unresolved.
  • No unifying model linking scaffolding to GTPase and Hippo regulation
  • Post-translational or conformational switches controlling PALS1 function not characterized
  • Direct human disease mutations causally tested in the corpus are limited

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0005198 structural molecule activity 3
Localization
GO:0005886 plasma membrane 6 GO:0005634 nucleus 1 GO:0005929 cilium 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1500931 Cell-Cell communication 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
CRB3EPB41L5EZRMPP3MPP4PAR6PARD3PATJ
Complex memberships
CRB3–PALS1–PATJ apical polarity complexPALS1–PATJ–MALS/Lin-7 L27 scaffoldPar6/Par3/aPKC complex (bridged via PALS1)

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 PALS1 L27N domain binds PATJ (mammalian Discs Lost homologue) via a unique Maguk recruitment domain, targeting PALS1 to tight junctions; PALS1 L27C domain binds mLin-7; and the PALS1 PDZ domain binds CRB1 (human Crumbs homologue), forming a conserved multiprotein polarity complex. Co-immunoprecipitation, pulldown assays, domain mapping, colocalization by confocal microscopy The Journal of cell biology High 11927608
2003 Overexpression of dominant-negative Myc-Lin-2-Pals1 chimera (PDZ domain of Pals1 replacing Lin-2 PDZ) in MDCK cells causes tight junction formation delays and apical polarity defects, demonstrating that the CRB3-Pals1 PDZ interaction is required for tight junction formation and epithelial polarization. Dominant-negative overexpression, calcium switch assay, MDCK cyst morphogenesis assay, confocal microscopy Journal of cell science High 12771187
2003 CRB3 (Crumbs3) interacts with PALS1 through its conserved intracellular domain, and this complex also includes PATJ; CRB3 localizes to the apical surface and tight junctions of epithelial cells. Co-immunoprecipitation, subcellular fractionation, confocal microscopy, mutagenesis of CRB3 intracellular domain Gene High 12527193
2004 siRNA-mediated knockdown of PALS1 in MDCKII cells causes loss of PATJ expression (a known binding partner), decreased association of CRB3 with Par6/Par3/aPKC complex, failure to recruit aPKC to tight junctions, delayed polarization after calcium switch, decreased transepithelial electrical resistance, and inability to form lumenal cysts. Stable siRNA knockdown, calcium switch assay, transepithelial electrical resistance measurement, 3D collagen cyst assay, confocal microscopy Molecular biology of the cell High 14718565
2004 Par-6 PDZ domain binds an internal (non-C-terminal) sequence in PALS1/Stardust amino terminus; crystal structure of the Par-6 PDZ-Pals1 complex shows the PDZ ligand-binding site is deformed to accommodate internal binding; Cdc42 binding to the Par-6 CRIB domain regulates C-terminal ligand binding but not Pals1 internal binding. Crystal structure determination, binding assays, mutagenesis Nature structural & molecular biology High 15475968
2004 Par-6 binds an evolutionarily conserved region in the amino terminus of PALS1 via the Par-6 PDZ domain; valine and aspartic acid residues in this PALS1 region are essential for the interaction; Par-6 and PATJ compete for binding to PALS1 (Par-6 interferes with PATJ binding) and do not act synergistically. Mutagenesis, GST pulldown, co-immunoprecipitation, competitive binding assays The Journal of biological chemistry High 15140881
2004 PALS1 interacts with the neuronal GABA transporter GAT1 via the PALS1 PDZ domain (identified by yeast two-hybrid and confirmed by co-immunoprecipitation in COS-7 cells); coexpression of PALS1 with GAT1 increases [3H]-GABA uptake by increasing GAT1 protein levels. Yeast two-hybrid, co-immunoprecipitation, [3H]-GABA uptake assay, immunofluorescence Molecular and cellular neurosciences Medium 15234345
2005 MPP5/PALS1 directly interacts with MPP4 via L27 heterodimerization; MPP4 is recruited to the CRB1 complex through its interaction with MPP5; all three proteins colocalize at the outer limiting membrane of the retina. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, immunohistochemistry, immunoelectron microscopy, 3D homology modeling Investigative ophthalmology & visual science High 15914641
2005 PALS1 interacts with ezrin via the ezrin N-terminus and PALS1 is required for apical localization of ezrin in gastric parietal cells; disruption of this interaction (by PALS1 suppression or deletion of PALS1-binding domain in ezrin) eliminates apical ezrin localization and impairs apical membrane remodeling during parietal cell secretion. Co-immunoprecipitation, siRNA knockdown, domain deletion, confocal microscopy, functional secretion assay The Journal of biological chemistry High 15677456
2005 NMR solution structures of the L27 domain complexes of Patj/Pals1 (and mLin-2/mLin-7) reveal a tetrameric assembly (two heterodimers); the C-terminal alpha-helix of each L27 domain forms a central helix bundle critical for partner specificity. NMR structure determination, biochemical binding assays, mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 15863617
2005 MPP5 (PALS1) and MPP4 localize to distinct sites in the mouse retina: MPP5 exclusively at apical outer limiting membrane junctions, MPP4 at photoreceptor synaptic terminals; MPP4 directly interacts with Veli proteins (Veli1, -3) via L27 heterodimerization in vitro, and Veli3 colocalizes with both MPP4 and MPP5. Immunofluorescence microscopy, L27 heterodimerization in vitro binding assay, antibody generation and immunohistochemistry The Journal of comparative neurology Medium 15558731
2005 In zebrafish, nagie oko (nok)/Mpp5 (PALS1 ortholog) is required tissue-autonomously within myocardial cells for polarized epithelial organization and coherence during heart cone formation, and for myocardial cell expansion during heart tube elongation; Has/PRKCi (aPKC) and Nok/Mpp5 act together in myocardial morphogenesis. Genetic epistasis in zebrafish, tissue-specific rescue experiments, confocal microscopy of myocardial cell organization Development (Cambridge, England) High 16319113
2006 MPP3 directly interacts with MPP5/PALS1 and is recruited to the CRB1/MPP5 scaffold at the outer limiting membrane of the retina; MPP3 also forms separate complexes with DLG1 at the outer plexiform layer. Co-immunoprecipitation, immunohistochemistry in human and mouse retinas, localization studies The FEBS journal Medium 16519681
2006 siRNA silencing of Pals1 in Müller glia cells results in loss of Crb1, Crb2, Mupp1, and Veli3 protein localization at the subapical region (SAR) and partial loss of Crb3, demonstrating that Pals1 is required for correct localization of Crb family members and associated proteins at the SAR of polarized Müller glia. RNAi knockdown in primary retinal cultures, immunoelectron microscopy, confocal microscopy Human molecular genetics High 16885194
2006 PALS1 knockdown in MDCK cells causes not only tight junction defects but also severe adherens junction defects; E-cadherin fails to be delivered to the cell surface and accumulates in peripheral puncta; the exocyst complex is mislocalized in PALS1 knockdown cells, suggesting PALS1 regulates E-cadherin trafficking via the exocyst. Stable siRNA knockdown, rescue with PALS1 mutants, E-cadherin surface biotinylation, confocal microscopy of exocyst and E-cadherin localization Molecular biology of the cell High 17182851
2007 EPB41L5 (a FERM domain protein) associates with the HOOK domain of MPP5/PALS1 and with the intracellular domains of all three Crumbs homologs via its FERM domain, forming a novel component of the mammalian CRB-MPP5 polarity complex; overexpression of EPB41L5 in MDCK cells disrupts ZO-1 and PATJ localization. Co-immunoprecipitation, co-expression studies, co-localization, overexpression functional assay in MDCK cells Experimental cell research Medium 17920587
2009 Nephrocystin-1 (NPHP1) and nephrocystin-4 (NPHP4) physically interact with PALS1, PATJ, and Par6; shRNA knockdown of NPHP1 or NPHP4 in MDCK cells phenocopies PALS1 depletion (delayed TJ formation, abnormal cilia, multi-lumen cysts), placing nephrocystins in the same polarity pathway as PALS1. Co-immunoprecipitation, shRNA knockdown, tight junction formation assay, 3D collagen matrix cyst assay, cilia analysis Human molecular genetics High 19755384
2010 The SARS-CoV E protein C-terminal PDZ-binding motif (last four amino acids) binds the PALS1 PDZ domain; in SARS-CoV-infected cells, PALS1 redistributes to the ERGIC/Golgi region where E accumulates; ectopic expression of E in MDCKII cells delays tight junction formation and disrupts polarity and PALS1 distribution in a PDZ-binding motif-dependent manner. Co-immunoprecipitation, GST pulldown, confocal microscopy in infected cells, MDCKII cyst morphogenesis assay, PDZ-binding motif mutant Molecular biology of the cell High 20861307
2010 Pals1 is required in myelinating Schwann cells for normal myelin sheath thickness and length; silencing of pals1 in vivo reduces myelin turns without grossly disrupting compact myelin; pals1 is required for polarized localization of vesicular markers sec8 and syntaxin4, and for distribution of E-cadherin, PMP22, and MAG at the plasma membrane, suggesting a role in membrane protein trafficking in Schwann cells. In vivo siRNA silencing in Schwann cells, electron microscopy, confocal microscopy, immunostaining for polarity and vesicular markers The Journal of neuroscience High 20237282
2011 PALS1 conditional knockdown in mice results in loss of Crumbs complex proteins at adherens junctions in the retina, progressive photoreceptor degeneration, abnormal retinal pigment epithelium structure, ectopic photoreceptors, and irregular outer limiting membrane, demonstrating an essential structural role for PALS1 in maintaining the CRB complex and retinal architecture. Conditional knockdown mouse model, electroretinography, confocal scanning laser ophthalmoscopy, optical coherence tomography, immunohistochemistry The Journal of neuroscience High 22114289
2011 PALS1 participates in TCR-mediated NF-κB activation in T lymphocytes; siRNA knockdown of PALS1 in Jurkat cells and primary T cells specifically impairs TCR-induced NF-κB activation and optimal lymphocyte proliferation. siRNA knockdown, NF-κB reporter assay, proliferation assay, RT-PCR, immunoblot PloS one Medium 21479189
2012 Deletion of Pals1 in retinal progenitor cells disrupts apical localization of Crb proteins and causes early visual impairment, disorganized retinal lamination, and retinal degeneration mimicking Leber congenital amaurosis; Pals1 and Crb proteins are functionally interdependent for apical localization. Conditional Pals1 knockout mouse, electroretinogram, confocal microscopy, immunohistochemistry Human molecular genetics High 22398208
2012 Crystal structure of L27 domain heterotrimer from Patj/Pals1/Mals2 reveals two cognate heterodimeric L27 pairs that assemble mutually independently, providing a novel mechanism for tandem L27 domain-mediated supramolecular complex assembly. Crystal structure determination, biochemical binding assays The Journal of biological chemistry High 22337881
2013 MPP3 directly interacts with PALS1/MPP5 and is required for maintaining proper levels of PALS1 at the subapical region adjacent to adherens junctions; loss of MPP3 in mice causes significant loss of PALS1 at the subapical region, and combined loss of MPP3 and Pals1 accelerates retinal degeneration. Conditional Mpp3 knockout mouse, immunofluorescence, co-immunoprecipitation, electroretinography, double-mutant genetic analysis Glia High 23893895
2014 Crystal structure of PALS1 PDZ-SH3-GK tandem bound to the Crumbs cytoplasmic tail (Crb-CT) shows the three domains form a structural supramodule; all three domains contribute to binding with ~70 nM affinity (~100-fold stronger than PDZ alone); mutations disrupting interdomain contacts weaken PALS1-Crb interaction and compromise PALS1-mediated polarity in MDCK cysts. Crystal structure determination, isothermal titration calorimetry, mutagenesis, MDCK cyst polarity assay Proceedings of the National Academy of Sciences of the United States of America High 25385611
2015 Crystal structures of the human PALS1 PDZ domain with and without Crumbs C-terminal ligand (ERLI) reveal a key Phe residue that gates access to the PDZ peptide-binding groove; removal of this gating residue enhances binding affinity by >5-fold, suggesting regulated access of Crumbs to Pals1. Crystallography, fluorescence polarization binding assay, mutagenesis Acta crystallographica. Section D, Biological crystallography High 25760605
2015 In Schwann cells, loss of Pals1 impairs radial sorting of axons, delays myelination, and reduces nerve conduction velocities; polyaxonal myelination persists in adult Pals1-deficient nerves; Pals1 interacts with Par3 and its loss reduces Par3 levels in Schwann cells; loss of Pals1 in oligodendrocytes does not affect CNS myelination. Conditional Pals1 knockout in Schwann cells and oligodendrocytes, nerve conduction velocity measurement, electron microscopy, Co-IP for Par3 interaction, immunofluorescence The Journal of neuroscience High 26203142
2015 In the Drosophila embryonic epidermis, Stardust (Drosophila Pals1) is essential for correct subcellular localization of PATJ; L27 domain of PATJ is required for its correct localization and function; PATJ associates with both Baz-Sdt and Crb-Sdt complexes in mature epithelium. Drosophila genetics, biochemical pulldown, immunofluorescence, domain mutagenesis The Journal of biological chemistry Medium 25847234
2015 Deletion of Pals1 in cerebellar progenitors causes severely undersized cerebellum with disrupted layers and reduced granule cell production; Pals1 maintains cerebellar progenitor pools by preventing premature differentiation; Pals1 acts epistatically to Shh signaling—activated Smo cannot overcome Pals1 loss. Conditional Pals1 knockout mouse, electroretinography, cell cycle gene expression analysis, genetic epistasis with Smo activation Development (Cambridge, England) High 26657772
2016 VE-cadherin directly interacts with Pals1 through a membrane-proximal motif in the VE-cadherin cytoplasmic domain; VE-cadherin clusters Pals1 at cell-cell junctions; mutation of the Pals1-binding motif in VE-cadherin abrogates VE-cadherin's ability to regulate apicobasal polarity and vascular lumen formation. Co-immunoprecipitation, pulldown, site-directed mutagenesis, vascular lumen formation assay, polarity assay in endothelial cells Molecular biology of the cell High 27466317
2017 Pals1 haploinsufficiency in mouse nephrons causes lethal cyst formation and proteinuria; in epithelial cell culture models, Pals1 functions as a dose-dependent upstream regulator of crosstalk between Hippo and TGF-β signaling pathways. Conditional heterozygous Pals1 knockout mouse, histology, signaling pathway analysis (Hippo/TGF-β), Drosophila nephrocyte analysis Journal of the American Society of Nephrology Medium 28154200
2021 Cryo-EM structure of PALS1-SARS-CoV-2 E protein complex shows the E protein C-terminal DLLV motif binds a pocket formed exclusively by hydrophobic residues from both the PDZ and SH3 domains of PALS1. Cryo-electron microscopy structure determination Nature communications High 34103506
2021 Crystal structures of PALS1 PDZ domain bound to SARS-CoV-1 and SARS-CoV-2 E protein PDZ-binding motifs show both viral peptides bind the PDZ domain with ~29.6 and ~22.8 μM affinity respectively; MERS-CoV C-terminal sequence does not bind PALS1 PDZ domain. Crystallography, surface plasmon resonance / fluorescence-based affinity measurements Communications biology High 34117354
2021 Loss of Pals1 in colorectal cancer cells increases Arf6 and Rac1 activity, enhancing cell migration, invasion, and metastasis in vivo; this function is independent of canonical PALS1 binding partners (PATJ, CRB3) and tight junction formation. Pals1 knockout/knockdown, Arf6 and Rac1 activity assays (GTP-pulldown), in vitro migration/invasion assay, in vivo tumor transplantation assay Molecular cancer High 33941200
2022 Angiomotin isoform 2 (Ap80) promotes binding of PALS1 to KIF13B at the base of the primary cilium; Ap80 concentrates at and recruits PALS1 to the ciliary base; Ap80 depletion causes ciliary elongation and reduced agonist-induced SMO accumulation in cilia. Co-immunoprecipitation, live-cell imaging, ciliary length measurement, SMO ciliary accumulation assay, siRNA knockdown Journal of cell science Medium 35673984
2022 Pals1 functions redundantly with the Arf6-GAP SMAP1 to inhibit Arf6 activity; in cells expressing SMAP1, loss of Pals1 disrupts tight junctions but does not increase Arf6/Rac1 activity or migration; only combined loss of both SMAP1 and Pals1 increases Arf6/Rac1 activity and cell migration. Pals1 and SMAP1 knockout/knockdown, Arf6/Rac1 activity assays, migration assay, patient cohort analysis Cancer gene therapy High 36494580
2023 In Pals1 cortical mutant mice, cell-in-cell (CIC) structures (entosis-like) form inside dividing cells, accompanied by lengthened mitosis and cytokinesis defects; ROCK inhibition abrogates CIC structures and restores normal mitosis length; genetic elimination of Trp53 rescues cortical size and reduces CIC structures, placing this entotic process downstream of Pals1 loss in microcephaly pathogenesis. Conditional Pals1 knockout mouse, ROCK inhibitor treatment, Trp53 genetic rescue, live imaging of cell division, electron microscopy Nature communications High 36604424
2024 PALS1 knockout in MDCKII cells causes redistribution of tight junction proteins from bicellular to tricellular contacts, increased paracellular permeability, delayed tight junction reassembly after Ca2+ removal or F-actin depolymerization, and redistribution of RhoA from junctions to cytosol; PALS1-dependent localization of TJ proteins at bicellular junctions requires its interaction with PATJ. CRISPR/Cas9 PALS1 knockout, transepithelial electrical resistance, confocal microscopy, Ca2+ switch assay, F-actin depolymerization/repolymerization assay, RhoA localization Journal of cell science High 38265145
2025 MPP5/PALS1 physically interacts with YAP and TAZ in liver cancer cells; the PDZ domain of PALS1 is required for YAP binding (shown by domain deletion Co-IP); PALS1 facilitates nuclear exclusion of YAP and TAZ; reduced PALS1 expression correlates with nuclear YAP/TAZ accumulation in HCC tissue. Co-immunoprecipitation, proximity ligation assay, PDZ domain deletion analysis, proteomics/functional screening International journal of molecular sciences Medium 39859373

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost. The Journal of cell biology 299 11927608
2010 The SARS coronavirus E protein interacts with PALS1 and alters tight junction formation and epithelial morphogenesis. Molecular biology of the cell 177 20861307
2003 The Crumbs3-Pals1 complex participates in the establishment of polarity in mammalian epithelial cells. Journal of cell science 176 12771187
2003 Mammalian Crumbs3 is a small transmembrane protein linked to protein associated with Lin-7 (Pals1). Gene 168 12527193
2004 Loss of PALS1 expression leads to tight junction and polarity defects. Molecular biology of the cell 153 14718565
2004 Internal recognition through PDZ domain plasticity in the Par-6-Pals1 complex. Nature structural & molecular biology 116 15475968
2006 Pals1/Mpp5 is required for correct localization of Crb1 at the subapical region in polarized Muller glia cells. Human molecular genetics 90 16885194
2009 Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6. Human molecular genetics 89 19755384
2004 Tight junction protein Par6 interacts with an evolutionarily conserved region in the amino terminus of PALS1/stardust. The Journal of biological chemistry 88 15140881
2021 Structural basis for SARS-CoV-2 envelope protein recognition of human cell junction protein PALS1. Nature communications 79 34103506
2005 Heart and soul/PRKCi and nagie oko/Mpp5 regulate myocardial coherence and remodeling during cardiac morphogenesis. Development (Cambridge, England) 72 16319113
2014 Structure of Crumbs tail in complex with the PALS1 PDZ-SH3-GK tandem reveals a highly specific assembly mechanism for the apical Crumbs complex. Proceedings of the National Academy of Sciences of the United States of America 71 25385611
2010 Pals1 is a major regulator of the epithelial-like polarization and the extension of the myelin sheath in peripheral nerves. The Journal of neuroscience : the official journal of the Society for Neuroscience 70 20237282
2006 PALS1 regulates E-cadherin trafficking in mammalian epithelial cells. Molecular biology of the cell 70 17182851
2005 MPP5 recruits MPP4 to the CRB1 complex in photoreceptors. Investigative ophthalmology & visual science 59 15914641
2020 Improved binding of SARS-CoV-2 Envelope protein to tight junction-associated PALS1 could play a key role in COVID-19 pathogenesis. Microbes and infection 56 32891874
2007 FERM protein EPB41L5 is a novel member of the mammalian CRB-MPP5 polarity complex. Experimental cell research 54 17920587
2021 Structural basis of coronavirus E protein interactions with human PALS1 PDZ domain. Communications biology 44 34117354
2020 Comparing the binding properties of peptides mimicking the Envelope protein of SARS-CoV and SARS-CoV-2 to the PDZ domain of the tight junction-associated PALS1 protein. Protein science : a publication of the Protein Society 44 32822073
2011 PALS1 is essential for retinal pigment epithelium structure and neural retina stratification. The Journal of neuroscience : the official journal of the Society for Neuroscience 44 22114289
2005 Membrane-associated guanylate kinase proteins MPP4 and MPP5 associate with Veli3 at distinct intercellular junctions of the neurosensory retina. The Journal of comparative neurology 38 15558731
2005 PALS1 specifies the localization of ezrin to the apical membrane of gastric parietal cells. The Journal of biological chemistry 38 15677456
2012 Genetic ablation of Pals1 in retinal progenitor cells models the retinal pathology of Leber congenital amaurosis. Human molecular genetics 34 22398208
2006 MPP3 is recruited to the MPP5 protein scaffold at the retinal outer limiting membrane. The FEBS journal 32 16519681
2017 Pals1 Haploinsufficiency Results in Proteinuria and Cyst Formation. Journal of the American Society of Nephrology : JASN 31 28154200
2005 A unified assembly mode revealed by the structures of tetrameric L27 domain complexes formed by mLin-2/mLin-7 and Patj/Pals1 scaffold proteins. Proceedings of the National Academy of Sciences of the United States of America 25 15863617
2015 Structures of the human Pals1 PDZ domain with and without ligand suggest gated access of Crb to the PDZ peptide-binding groove. Acta crystallographica. Section D, Biological crystallography 20 25760605
2010 Polycystin-2 activity is controlled by transcriptional coactivator with PDZ binding motif and PALS1-associated tight junction protein. The Journal of biological chemistry 19 20833712
2015 The Polarity Protein Pals1 Regulates Radial Sorting of Axons. The Journal of neuroscience : the official journal of the Society for Neuroscience 18 26203142
2016 VE-cadherin interacts with cell polarity protein Pals1 to regulate vascular lumen formation. Molecular biology of the cell 16 27466317
2004 The GABA transporter GAT1 and the MAGUK protein Pals1: interaction, uptake modulation, and coexpression in the brain. Molecular and cellular neurosciences 16 15234345
2015 Localization and Function of Pals1-associated Tight Junction Protein in Drosophila Is Regulated by Two Distinct Apical Complexes. The Journal of biological chemistry 15 25847234
2012 Structure of an L27 domain heterotrimer from cell polarity complex Patj/Pals1/Mals2 reveals mutually independent L27 domain assembly mode. The Journal of biological chemistry 15 22337881
2021 Pals1 prevents Rac1-dependent colorectal cancer cell metastasis by inhibiting Arf6. Molecular cancer 14 33941200
2021 Structural determinants driving the binding process between PDZ domain of wild type human PALS1 protein and SLiM sequences of SARS-CoV E proteins. Computational and structural biotechnology journal 13 33758649
2013 MPP3 regulates levels of PALS1 and adhesion between photoreceptors and Müller cells. Glia 12 23893895
2015 The apical complex protein Pals1 is required to maintain cerebellar progenitor cells in a proliferative state. Development (Cambridge, England) 11 26657772
2023 An entosis-like process induces mitotic disruption in Pals1 microcephaly pathogenesis. Nature communications 10 36604424
2023 Circulating and Endometrial Profiles of miR-145, miR-155-5p, miR-224, MPP-5, and PECAM-1 Expression in Patients with Repeated Implantation Failure: A Case Control Study. Cell journal 9 37434460
2022 Angiomotin isoform 2 promotes binding of PALS1 to KIF13B at primary cilia and regulates ciliary length and signaling. Journal of cell science 9 35673984
2020 De novo variants in MPP5 cause global developmental delay and behavioral changes. Human molecular genetics 9 33073849
2011 Participation of the cell polarity protein PALS1 to T-cell receptor-mediated NF-κB activation. PloS one 9 21479189
2024 PALS1 is a key regulator of the lateral distribution of tight junction proteins in renal epithelial cells. Journal of cell science 6 38265145
2020 C. elegans MAGU-2/Mpp5 homolog regulates epidermal phagocytosis and synapse density. Journal of neurogenetics 5 32366143
2022 Impact of Pals1 on Expression and Localization of Transporters Belonging to the Solute Carrier Family. Frontiers in molecular biosciences 3 35252349
2025 The Cell Polarity Protein MPP5/PALS1 Controls the Subcellular Localization of the Oncogenes YAP and TAZ in Liver Cancer. International journal of molecular sciences 2 39859373
2023 A case of a childhood onset developmental encephalopathy with a novel de novo truncating variant in the Membrane Protein Palmitoylated 5 (MPP5) gene. Seizure 2 36710240
2022 Pals1 functions in redundancy with SMAP1 to inhibit Arf6 in order to prevent Rac1-dependent colorectal cancer cell migration and invasion. Cancer gene therapy 2 36494580
2024 Investigation of the Mutations in the SARS-CoV-2 Envelope Protein and Its Interaction with the PALS1 by Molecular Docking. Reports of biochemistry & molecular biology 1 39582830
2011 Crystallization and preliminary X-ray data collection of the L27(PATJ)-(L27N,L27C)(Pals1)-L27(MALS) tripartite complex. Acta crystallographica. Section F, Structural biology and crystallization communications 1 22102253
2024 PALS1-dependent modulations of mRNA profiles in MDCK II cells grown in non-confluent monolayers and three-dimensional cysts. BMC genomic data 0 39614182

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