ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structure of Crumbs tail in complex with the PALS1 PDZ-SH3-GK tandem reveals a highly specific assembly mechanism for the apical Crumbs complex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 85 citations in OpenAlex.
- Bulk delivery of a preassembled apical surface initiates epithelial lumen formation.Nature communications · 2026Article
- Crumbs2 acts as a dynamic cellular sensor triggering stable podocyte cell-matrix anchorage.Biophysical journal · 2026Article
- A direct interaction of JAM-C with the tight junction scaffold protein ZO-2.Scientific reports · 2026Article
- Fasciclin 2 Cooperates with Discs Large to Maintain Epithelial Architecture.bioRxiv : the preprint server for biology · 2026Article
- Patient-Derived Variants Define Constraints for Ligand Binding at the PDZ Domain of CASK.Journal of neurochemistry · 2025Article
- PALS1-dependent modulations of mRNA profiles in MDCK II cells grown in non-confluent monolayers and three-dimensional cysts.BMC genomic data · 2024Article
- A size filter at the Golgi regulates apical membrane protein sorting.Nature cell biology · 2024Article
- Article
- Genetic evidence for splicing-dependent structural and functional plasticity in CASK protein.Journal of medical genetics · 2024Article
- Intestinal mRNA expression analysis of polarity-related genes identified the discriminatory ability of CRB3 as a diagnostic marker for celiac disease.Immunity, inflammation and disease · 2024Article
- A de novo missense mutation in MPP2 confers an increased risk of Vogt-Koyanagi-Harada disease as shown by trio-based whole-exome sequencing.Cellular & molecular immunology · 2023Article
- SARS-CoV-2 E protein: Pathogenesis and potential therapeutic development.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Review
- Super-resolution imaging uncovers the nanoscopic segregation of polarity proteins in epithelia.eLife · 2022Article
- Regulation of Liprin-α phase separation by CASK is disrupted by a mutation in its CaM kinase domain.Life science alliance · 2022Article
- Identification and characterization of Crumbs polarity complex proteins in Caenorhabditis elegans.The Journal of biological chemistry · 2022Article
- The Non-Linear Path from Gene Dysfunction to Genetic Disease: Lessons from the MICPCH Mouse Model.Cells · 2022Review
- Structural biology of SARS-CoV-2: open the door for novel therapies.Signal transduction and targeted therapy · 2022Review
- Case Report: Identification of a novelFrontiers in genetics · 2022Article
- Targeting PDZ domains as potential treatment for viral infections, neurodegeneration and cancer.Biology direct · 2021Review
- Structural basis of coronavirus E protein interactions with human PALS1 PDZ domain.Communications biology · 2021Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
The Crumbs (Crb) complex, formed by Crb, PALS1, and PATJ, is evolutionarily conserved in metazoans and acts as a master cell-growth and -polarity regulator at the apical membranes in polarized epithelia. Crb intracellular functions, including its direct binding to PALS1, are mediated by Crb's highly conserved 37-residue cytoplasmic tail. However, the mechanistic basis governing the highly specific Crb-PALS1 complex formation is unclear, as reported interaction between the Crb tail (Crb-CT) and PALS1 PSD-95/DLG/ZO-1 (PDZ) domain is weak and promiscuous. Here we have discovered that the PDZ-Src homolgy 3 (SH3)-Guanylate kinase (GK) tandem of PALS1 binds to Crb-CT with a dissociation constant of 70 nM, which is ∼ 100-fold stronger than the PALS1 PDZ-Crb-CT interaction. The crystal structure of the PALS1 PDZ-SH3-GK-Crb-CT complex reveals that PDZ-SH3-GK forms a structural supramodule with all three domains contributing to the tight binding to Crb. Mutations disrupting the tertiary interactions of the PDZ-SH3-GK supramodule weaken the PALS1-Crb interaction and compromise PALS1-mediated polarity establishment in Madin-Darby canine kidney (MDCK) cysts. We further show that specific target binding of other members of membrane-associated guanylate kinases (MAGUKs) (e.g., CASK binding to neurexin) also requires the presence of their PDZ-SH3-GK tandems.
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