ArticleCirculation research2019
Talin-Dependent Integrin Activation Regulates VE-Cadherin Localization and Endothelial Cell Barrier Function.
Article in Circulation research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 94 citations in OpenAlex.
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- Talin1 modulates the Piezo1-YAP axis to regulate endothelial cell inflammation and atherosclerosis.Cellular and molecular life sciences : CMLS · 2025Article
- De novo talin-1 variant L353F connects multifaceted clinical symptoms to alterations in talin-1 function.The Biochemical journal · 2025Article
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- The impact of a high fat diet and platelet activation on pre-metastatic niche formation.Nature communications · 2025Article
- Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.Biomarker research · 2025Review
- Talin, a Rap1 effector for integrin activation at the plasma membrane, also promotes Rap1 activity by disrupting sequestration of Rap1 by SHANK3.Journal of cell science · 2025Article
- Exosomes in arteriovenous fistula stenosis.Frontiers in cell and developmental biology · 2025Review
- Acetaminophen Overdose Reveals PAR4 as a Low-Expressing but Potent Receptor on the Hepatic Endothelium in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Article
- Apical integrins as a switchable target to regulate the epithelial barrier.Journal of cell science · 2024Article
- Talin-1 variants associated with spontaneous coronary artery dissection (SCAD) highlight how even subtle changes in multi-functional scaffold proteins can manifest in disease.Human molecular genetics · 2024Article
- Crosstalk Among Glial Cells in the Blood-Brain Barrier Injury After Ischemic Stroke.Molecular neurobiology · 2024Review
- Neutrophil extracellular traps induce intrahepatic thrombotic tendency and liver damage in cholestatic liver disease.Hepatology communications · 2024Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
rationaleEndothelial barrier function depends on the proper localization and function of the adherens junction protein VE (vascular endothelial)-cadherin. Previous studies have suggested a functional relationship between integrin-mediated adhesion complexes and VE-cadherin yet the underlying molecular links are unclear. Binding of the cytoskeletal adaptor protein talin to the β-integrin cytoplasmic domain is a key final step in regulating the affinity of integrins for extracellular ligands (activation) but the role of integrin activation in VE-cadherin mediated endothelial barrier function is unknown.
objectiveTo test the requirement of talin-dependent activation of β1 integrin in VE-cadherin organization and endothelial cell (EC) barrier function. METHODS AND
resultsEC-specific deletion of talin in adult mice resulted in impaired stability of intestinal microvascular blood vessels, hemorrhage, and death. Talin-deficient endothelium showed altered VE-cadherin organization at EC junctions in vivo. shRNA (short hairpin RNA)-mediated knockdown of talin1 expression in cultured ECs led to increased radial actin stress fibers, increased adherens junction width and increased endothelial monolayer permeability measured by electrical cell-substrate impedance sensing. Restoring β1-integrin activation in talin-deficient cells with a β1-integrin activating antibody normalized both VE-cadherin organization and EC barrier function. In addition, VE-cadherin organization was normalized by reexpression of talin or integrin activating talin head domain but not a talin head domain mutant that is selectively deficient in activating integrins.
conclusionsTalin-dependent activation of EC β1-integrin stabilizes VE-cadherin at endothelial junctions and promotes endothelial barrier function.
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