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Related Concept Videos

Tight Junctions01:29

Tight Junctions

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Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
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Anchoring Junctions01:03

Anchoring Junctions

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Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
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Laminins are the Adhesive Proteins of Basal Lamina00:55

Laminins are the Adhesive Proteins of Basal Lamina

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Laminins are heterotrimeric proteins with high molecular mass found in the extracellular matrix. Each laminin molecule is composed of three chains, viz. alpha, beta, and gamma, coded by five, four, and three paralogous genes, respectively. Laminins are categories based on the compositions of the three chains.
In humans, the five forms of alpha chains are LAMA 1, LAMA 2, LAMA 3, LAMA 4, and LAMA 5. The four forms of beta chains are LAMB 1, LAMB 2, LAMB 3, and LAMB 4. The three forms of gamma...
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Type IV Collagen of Basal Lamina01:05

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Type IV collagen is a 400 nm long, network-forming collagen that acts as a barrier between the epithelial and endothelial cells. Type IV collagen  forms the backbone of the basement membrane by scaffolding with laminin, entactin, proteoglycans, and fibronectin. Apart from rendering structural support to the basement membrane, it also helps entail signaling potentials necessary for both pathological and physiological functions.
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Basal Lamina are the Specialized Form of ECM01:03

Basal Lamina are the Specialized Form of ECM

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The basal lamina is a thin extracellular layer that lies underneath the cells and separates them from other tissues. The three layers of the basal lamina are lamina lucida, lamina densa and lamina reticularis. The basal lamina, a mixture of glycoproteins and collagen, provides an attachment site for the epithelium, separating it from underlying connective tissue. The framework of basal lamina has other essential proteins such as laminins mesh, perlecan, entactin, and type IV collagen.
Proteins...
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Adherens Junctions01:24

Adherens Junctions

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Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types –  adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as  epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as  heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
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Updated: Sep 9, 2025

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Basal IFN-λ2/3 expression mediates tight junction formation in human epithelial cells.

Yagmur Keser1, Camila Metz-Zumaran1,2, Zina M Uckeley1

  • 1Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA.

The EMBO Journal
|September 1, 2025
PubMed
Summary

Basal type-III interferon (IFN-λ) expression is crucial for epithelial barrier integrity, promoting tight junction formation. This expression relies on cGAS-STING signaling and is regulated by the Hippo pathway.

Keywords:
Basal IFNλ SignalingEpithelial Barrier FunctionHippo Signaling PathwayTight JunctionscGAS-STING Pathway

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Area of Science:

  • Immunology
  • Cell Biology
  • Epithelial Biology

Background:

  • Type-III interferons (IFN-λs) are vital for antiviral defense and maintaining intestinal epithelial barrier function.
  • Basal IFN-λ expression occurs even without pathogens, but its regulation and function remain unclear.

Purpose of the Study:

  • To elucidate the mechanisms regulating basal IFN-λ expression.
  • To determine the functional role of basal IFN-λ expression in epithelial barrier development and maintenance.

Main Methods:

  • Investigated basal IFN-λ2/3 expression in cellular epithelium.
  • Utilized cGAS-STING and Hippo pathway signaling analysis.
  • Assessed epithelial barrier function, tight junction formation, and Claudin-2 expression.

Main Results:

  • Basal IFN-λ2/3 expression correlates with intact epithelial tight junctions and barrier function.
  • Expression depends on cGAS-STING-mediated mitochondrial DNA detection.
  • The Hippo pathway inhibits basal IFN-λ2/3 at low cell densities.
  • IFN-λ2/3 suppresses Claudin-2, promoting barrier formation during cell confluency.
  • Absence of basal IFN-λ2/3 impairs tight junction development and barrier function.

Conclusions:

  • Basal IFN-λ2/3 expression is essential for proper epithelial barrier formation and integrity.
  • This pathway is regulated by cellular density and intrinsic signaling pathways (cGAS-STING, Hippo).
  • IFN-λs play a critical role in maintaining epithelial homeostasis under steady-state conditions, beyond pathogen defense.