ArticleThe Journal of biological chemistry2022
Cingulin binds to the ZU5 domain of scaffolding protein ZO-1 to promote its extended conformation, stabilization, and tight junction accumulation.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- A direct interaction of JAM-C with the tight junction scaffold protein ZO-2.Scientific reports · 2026Article
- Lactobacillus yoelii Lac-2 mediates the mechanism of MAPK signaling pathway involved in the regulation of intestinal barrier and pathogen translocation by Zonulin expression.Scientific reports · 2026Article
- Coffea arabica pulp aqueous extract exhibits the anti-colitogenic effect in mice: preventive efficacy and possible mechanisms of action.Biological research · 2026Article
- ZO-1 shuttles between apical junctional complexes and podosomes by riding ERK activation waves.Nature communications · 2026Article
- Brain neurovascular unit in response to intra- and extra-central nervous system cancers: implications, mechanisms, and challenges.Cancer cell international · 2025Review
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- Article
- A feedback circuitry involving γ-actin, β-actin and nonmuscle myosin-2 A controls tight junction and apical cortex mechanics.Nature communications · 2025Article
- The epithelial barrier: a Janus-faced regulator in allergic airway diseases from defense to inflammation.Frontiers in allergy · 2025Review
- Paracingulin controls the junctional accumulation of nonmuscle myosin-2 in endothelial cells in vivo.microPublication biology · 2025Article
- Tight junction proteins in glial tumors development and progression.Frontiers in cellular neuroscience · 2025Review
- Cingulin-nonmuscle myosin interaction plays a role in epithelial morphogenesis and cingulin nanoscale organization.Journal of cell science · 2024Article
- A short guide to the tight junction.Journal of cell science · 2024Review
- Paracingulin recruits CAMSAP3 to tight junctions and regulates microtubule and polarized epithelial cell organization.Journal of cell science · 2024Article
- The Role of ZO-2 in Modulating JAM-A and γ-Actin Junctional Recruitment, Apical Membrane and Tight Junction Tension, and Cell Response to Substrate Stiffness and Topography.International journal of molecular sciences · 2024Article
- Functional Analysis of Membrane-Associated Scaffolding Tight Junction (TJ) Proteins in Tumorigenic Characteristics of B16-F10 Mouse Melanoma Cells.International journal of molecular sciences · 2024Article
- Lycopene Maintains Mitochondrial Homeostasis to Counteract the Enterotoxicity of Deoxynivalenol.Antioxidants (Basel, Switzerland) · 2023Article
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- Cingulin and paracingulin tether myosins-2 to junctions to mechanoregulate the plasma membrane.The Journal of cell biology · 2023Article
- The CLDN5 gene at the blood-brain barrier in health and disease.Fluids and barriers of the CNS · 2023Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Zonula occludens-1 (ZO-1), the major scaffolding protein of tight junctions (TJs), recruits the cytoskeleton-associated proteins cingulin (CGN) and paracingulin (CGNL1) to TJs by binding to their N-terminal ZO-1 interaction motif. The conformation of ZO-1 can be either folded or extended, depending on cytoskeletal tension and intramolecular and intermolecular interactions, and only ZO-1 in the extended conformation recruits the transcription factor DbpA to TJs. However, the sequences of ZO-1 that interact with CGN and CGNL1 and the role of TJ proteins in ZO-1 TJ assembly are not known. Here, we used glutathione-S-transferase pulldowns and immunofluorescence microscopy to show that CGN and CGNL1 bind to the C-terminal ZU5 domain of ZO-1 and that this domain is required for CGN and CGNL1 recruitment to TJs and to phase-separated ZO-1 condensates in cells. We show that KO of CGN, but not CGNL1, results in decreased accumulation of ZO-1 at TJs. Furthermore, ZO-1 lacking the ZU5 domain showed decreased accumulation at TJs, was detectable along lateral contacts, had a higher mobile fraction than full-length ZO-1 by fluorescence recovery after photobleaching analysis, and had a folded conformation, as determined by structured illumination microscopy of its N-terminal and C-terminal ends. The CGN-ZU5 interaction promotes the extended conformation of ZO-1, since binding of the CGN-ZO-1 interaction motif region to ZO-1 resulted in its interaction with DbpA in cells and in vitro. Together, these results show that binding of CGN to the ZU5 domain of ZO-1 promotes ZO-1 stabilization and accumulation at TJs by promoting its extended conformation.
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