ArticleMolecular biology of the cell2015
A complex of ZO-1 and the BAR-domain protein TOCA-1 regulates actin assembly at the tight junction.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 66 citations in OpenAlex.
- Actin polymerization drives endogenous MMP-9 upregulation and blood-brain barrier disruption in ischemic brain endothelial cells.Molecular and cellular biochemistry · 2026Article
- The Effect of Pediococcus Lactis and Postbiotics on Gut Health and Intestinal Metabolic Profiles.Nutrients · 2026Article
- Tight junction dysfunction and cytoskeletal remodeling in Hirschsprung‑associated enterocolitis: A decade of mechanistic insights and therapeutic prospects (Review).Molecular medicine reports · 2026Review
- Proximity proteomics provides a new resource for exploring the function of Afadin and the complexity of cell-cell adherens junctions.Biology open · 2025Article
- Targeting Intestinal Permeability for Graft-versus-Host Disease Treatment: A Therapeutic Perspective with Defibrotide.Journal of experimental pharmacology · 2025Article
- Proximity proteomics provides a new resource for exploring the function of Afadin and the complexity of cell-cell adherens junctions.bioRxiv : the preprint server for biology · 2024Article
- Microsporidia persistence in host impairs epithelial barriers and increases chances of inflammatory bowel disease.Microbiology spectrum · 2024Article
- Systematic Study of Paeonol/Madecassoside Co-Delivery Nanoemulsion Transdermal Delivery System for Enhancing Barrier Repair and Anti-Inflammatory Efficacy.Molecules (Basel, Switzerland) · 2023Article
- Breaking the Gingival Barrier in Periodontitis.International journal of molecular sciences · 2023Review
- Mapping of the podocin proximity-dependent proteome reveals novel components of the kidney podocyte foot process.Frontiers in cell and developmental biology · 2023Article
- Tight junction proteins occludin and ZO-1 as regulators of epithelial proliferation and survival.Annals of the New York Academy of Sciences · 2022Review
- Tight junction channel regulation by interclaudin interference.Nature communications · 2022Article
- Gelsolin impairs barrier function in pancreatic ductal epithelial cells by actin filament depolymerization in hypertriglyceridemia-induced pancreatitisExperimental and therapeutic medicine · 2022Article
- Simple graphical approach to investigate differences in transepithelial paracellular leak pathway permeability.Physiological reports · 2022Article
- The Role of Cytoskeletal Proteins in the Formation of a Functional In Vitro Blood-Brain Barrier Model.International journal of molecular sciences · 2022Article
- T cell protein tyrosine phosphatase protects intestinal barrier function by restricting epithelial tight junction remodeling.The Journal of clinical investigation · 2021Article
- The Epithelial Cell Leak Pathway.International journal of molecular sciences · 2021Review
- Mixtures of natural antimicrobials can reduce Campylobacter jejuni, Salmonella enterica and Clostridium perfringens infections and cellular inflammatory response in MDCK cells.Gut pathogens · 2021Article
- The Arp2/3 Inhibitory Protein Arpin Is Required for Intestinal Epithelial Barrier Integrity.Frontiers in cell and developmental biology · 2021Article
- Ruffles and spikes: Control of tight junction morphology and permeability by claudins.Biochimica et biophysica acta. Biomembranes · 2020Review
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Assembly and sealing of the tight junction barrier are critically dependent on the perijunctional actin cytoskeleton, yet little is known about physical and functional links between barrier-forming proteins and actin. Here we identify a novel functional complex of the junction scaffolding protein ZO-1 and the F-BAR-domain protein TOCA-1. Using MDCK epithelial cells, we show that an alternative splice of TOCA-1 adds a PDZ-binding motif, which binds ZO-1, targeting TOCA-1 to barrier contacts. This isoform of TOCA-1 recruits the actin nucleation-promoting factor N-WASP to tight junctions. CRISPR-Cas9-mediated knockout of TOCA-1 results in increased paracellular flux and delayed recovery in a calcium switch assay. Knockout of TOCA-1 does not alter FRAP kinetics of GFP ZO-1 or occludin, but longer term (12 h) time-lapse microscopy reveals strikingly decreased tight junction membrane contact dynamics in knockout cells compared with controls. Reexpression of TOCA-1 with, but not without, the PDZ-binding motif rescues both altered flux and membrane contact dynamics. Ultrastructural analysis shows actin accumulation at the adherens junction in TOCA-1-knockout cells but unaltered freeze-fracture fibril morphology. Identification of the ZO-1/TOCA-1 complex provides novel insights into the underappreciated dependence of the barrier on the dynamic nature of cell-to-cell contacts and perijunctional actin.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.