ArticleMolecular biology of the cell2013
JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
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Who cites it
82 citing papers in PubMed, 127 citations in OpenAlex.
- Tight junction structure, assembly and (dys)function.Nature reviews. Molecular cell biology · 2026Review
- A direct interaction of JAM-C with the tight junction scaffold protein ZO-2.Scientific reports · 2026Article
- The role of Junctional Adhesion Molecule-A (JAM-A) in breast cancer metastasis.Molecular biology reports · 2026Review
- Food-derived molecules as regulators of intestinal tight junctions and barrier function: mechanisms and implications.Frontiers in drug delivery · 2026Review
- Article
- Junctional adhesion molecule-C: A multifunctional mediator of cell adhesion.Cellular and molecular life sciences : CMLS · 2025Review
- Looking Inside of the Intestinal Permeability Regulation by Protein-Derivatives from Bovine Milk.Molecular nutrition & food research · 2024Review
- Nanostructure-Mediated Transport of Therapeutics through Epithelial Barriers.International journal of molecular sciences · 2024Review
- 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
- A Review of a Breakdown in the Barrier: Tight Junction Dysfunction in Dental Diseases.Clinical, cosmetic and investigational dentistry · 2024Review
- RhoGDI1 regulates cell-cell junctions in polarized epithelial cells.Frontiers in cell and developmental biology · 2024Article
- Review
- D-2-hydroxyglutarate regulates human brain vascular endothelial cell proliferation and barrier function.Journal of neuropathology and experimental neurology · 2023Article
- Cell-cell communications: new insights into targeting efficacy of phytochemical adjuvants on tight junctions and pathophysiology of various malignancies.Journal of cell communication and signaling · 2023Review
- Roles of the ACE/Ang II/AT1R pathway, cytokine release, and alteration of tight junctions in COVID-19 pathogenesis.Tissue barriers · 2023Article
- Structure Composition and Intracellular Transport of Clathrin-Mediated Intestinal Transmembrane Tight Junction Protein.Inflammation · 2023Review
- Gut-Liver Axis and Non-Alcoholic Fatty Liver Disease: A Vicious Circle of Dysfunctions Orchestrated by the Gut Microbiome.Biology · 2022Review
- Epithelial JAM-A is fundamental for intestinal wound repair in vivo.JCI insight · 2022Article
- Junctional adhesion molecule-A deletion increases phagocytosis and improves survival in a murine model of sepsis.JCI insight · 2022Article
- Afadin couples RAS GTPases to the polarity rheostat Scribble.Nature communications · 2022Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Intestinal barrier function is regulated by epithelial tight junctions (TJs), structures that control paracellular permeability. Junctional adhesion molecule-A (JAM-A) is a TJ-associated protein that regulates barrier; however, mechanisms linking JAM-A to epithelial permeability are poorly understood. Here we report that JAM-A associates directly with ZO-2 and indirectly with afadin, and this complex, along with PDZ-GEF1, activates the small GTPase Rap2c. Supporting a functional link, small interfering RNA-mediated down-regulation of the foregoing regulatory proteins results in enhanced permeability similar to that observed after JAM-A loss. JAM-A-deficient mice and cultured epithelial cells demonstrate enhanced paracellular permeability to large molecules, revealing a potential role of JAM-A in controlling perijunctional actin cytoskeleton in addition to its previously reported role in regulating claudin proteins and small-molecule permeability. Further experiments suggest that JAM-A does not regulate actin turnover but modulates activity of RhoA and phosphorylation of nonmuscle myosin, both implicated in actomyosin contraction. These results suggest that JAM-A regulates epithelial permeability via association with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and control contraction of the apical cytoskeleton.
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Registered trials
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.