ArticleMucosal immunology2017
Cortactin deficiency causes increased RhoA/ROCK1-dependent actomyosin contractility, intestinal epithelial barrier dysfunction, and disproportionately severe DSS-induced colitis.
Article in Mucosal immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 63 citations in OpenAlex.
- NEK7 phosphorylation of cortactin modulates the migratory capacity of cells expressing EML4-ALK V3.Scientific reports · 2026Article
- The epithelial barrier theory proposes a comprehensive explanation for the origins of allergic and other chronic noncommunicable diseases.FEBS letters · 2025Review
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Cortactin-dependent control of Par1b-regulated epithelial cell polarity inCell insight · 2024Article
- Cortactin is in a complex with VE-cadherin and is required for endothelial adherens junction stability through Rap1/Rac1 activation.Scientific reports · 2024Article
- Coactosin-like protein 1 regulates integrity and repair of model intestinal epithelial barriers via actin binding dependent and independent mechanisms.Frontiers in cell and developmental biology · 2024Article
- Role of Rho GTPases in inflammatory bowel disease.Cell death discovery · 2023Review
- Bamboo Shoot andCurrent issues in molecular biology · 2022Article
- Spef1/CLAMP binds microtubules and actin-based structures and regulates cell migration and epithelia cell polarity.Annals of the New York Academy of Sciences · 2022Review
- Respiratory syncytial virus disrupts the airway epithelial barrier by decreasing cortactin and destabilizing F-actin.Journal of cell science · 2022Article
- Cortactin loss protects against hemin-induced acute lung injury in sickle cell disease.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- A cortactin CTTN coding SNP contributes to lung vascular permeability and inflammatory disease severity in African descent subjects.Translational research : the journal of laboratory and clinical medicine · 2022Article
- The Actin-Binding Protein Cortactin Promotes Sepsis Severity by Supporting Excessive Neutrophil Infiltration into the Lung.Biomedicines · 2022Article
- Receptor binding domain of SARS-CoV-2 is a functional αv-integrin agonist.bioRxiv : the preprint server for biology · 2022Article
- HS1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damage.European journal of cell biology · 2022Article
- Article
- An Integrated Proteomics and Metabolomics Strategy for the Mechanism of Calcium Oxalate Crystal-Induced Kidney Injury.Frontiers in medicine · 2022Article
- 3,4-Methylenedioxy-β-Nitrostyrene Alleviates Dextran Sulfate Sodium-Induced Mouse Colitis by Inhibiting the NLRP3 Inflammasome.Frontiers in pharmacology · 2022Article
- CSE/HFrontiers in immunology · 2022Article
- Cortactin Is Required for Efficient FAK, Src and Abl Tyrosine Kinase Activation and Phosphorylation ofInternational journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intestinal epithelium constitutes a first line of defense of the innate immune system. Epithelial dysfunction is a hallmark of intestinal disorders such as inflammatory bowel diseases (IBDs). The actin cytoskeleton controls epithelial barrier integrity but the function of actin regulators such as cortactin is poorly understood. Given that cortactin controls endothelial permeability, we hypothesized that cortactin is also important for epithelial barrier regulation. We found increased permeability in the colon of cortactin-KO mice that was accompanied by reduced levels of ZO-1, claudin-1, and E-cadherin. By contrast, claudin-2 was upregulated. Cortactin deficiency increased RhoA/ROCK1-dependent actomyosin contractility, and inhibition of ROCK1 rescued the barrier defect. Interestingly, cortactin deficiency caused increased epithelial proliferation without affecting apoptosis. KO mice did not develop spontaneous colitis, but were more susceptible to dextran sulfate sodium colitis and showed severe colon tissue damage and edema formation. KO mice with colitis displayed strong mucus deposition and goblet cell depletion. In healthy human colon tissues, cortactin co-localized with ZO-1 at epithelial cell contacts. In IBDs patients, we observed decreased cortactin levels and loss of co-localization with ZO-1. Thus, cortactin is a master regulator of intestinal epithelial barrier integrity in vivo and could serve as a suitable target for pharmacological intervention in IBDs.
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