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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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Overview of Cell-Cell Junctions01:14

Overview of Cell-Cell Junctions

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The complex three-dimensional arrangement of cells in any multicellular organism is defined and maintained by interactions of cells with each other and the extracellular matrix. Cell-cell junctions are specialized structures where the multi-protein complexes on one cell interact with the multi-protein complexes on another  cell. These cell junctions are classified  into three main types based on their function — occluding, anchoring, and gap junctions.
Occluding or Tight...
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Tension Response at Adherens Junctions01:26

Tension Response at Adherens Junctions

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The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
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Contact-dependent Signaling01:19

Contact-dependent Signaling

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Contact-dependent signaling, as the name suggests, requires that communicating cells be in direct contact with each other. This is achieved either through receptor-ligand interactions or by specialized cytoplasmic channels that allow the flow of small molecules between cells. In animal cells, channels called gap junctions facilitate contact-dependent signaling in certain tissues, whereas, plasmodesmata perform a similar function in plants.
Gap Junctions
In animal cells, gap junctions are formed...
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Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Gap Junctions01:27

Gap Junctions

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The cytoplasm of adjacent animal cells can exchange small molecules, ions, and secondary messengers via the communication channels which form the gap junctions. These junctions comprise a few hundred to thousands of molecular channels, each made of two halves, called the connexon hemichannel. A connexon is a hexamer of six transmembrane connexin proteins, which assemble radially, thus forming a pore or channel in the center. One connexon hemichannel docks with a corresponding connexon on the...
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Related Experiment Video

Updated: Sep 6, 2025

Functional Assessment of Intestinal Tight Junction Barrier and Ion Permeability in Native Tissue by Ussing Chamber Technique
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Functional Assessment of Intestinal Tight Junction Barrier and Ion Permeability in Native Tissue by Ussing Chamber Technique

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Tight junction channel regulation by interclaudin interference.

Nitesh Shashikanth1, Marion M France1, Ruyue Xiao1

  • 1Laboratory of Mucosal Barrier Pathobiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Nature Communications
|June 30, 2022
PubMed
Summary
This summary is machine-generated.

Barrier-forming claudin-4 inhibits cation channels by disrupting pore-forming claudins. This interclaudin interference mechanism reveals a new way tight junctions regulate paracellular permeability.

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Analysis of Protein-protein Interactions and Co-localization Between Components of Gap, Tight, and Adherens Junctions in Murine Mammary Glands
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Area of Science:

  • Cell biology
  • Biochemistry
  • Physiology

Background:

  • Tight junctions form selective seals in the paracellular space.
  • Claudin proteins are key to tight junction barrier and permeability functions.
  • Claudins are classified as pore-forming or barrier-forming.

Purpose of the Study:

  • To investigate the mechanism by which barrier-forming claudin-4 regulates paracellular permeability.
  • To determine claudin-4's role in the presence or absence of pore-forming claudins.
  • To elucidate the structural interactions between claudin-4 and other claudins.

Main Methods:

  • Claudin-4 knockout and overexpression studies.
  • Flux assays across cation channels formed by claudins 2 or 15.
  • Analysis of claudin polymerization and structural organization in nonepithelial cells.

Main Results:

  • Claudin-4 knockout/overexpression had minimal effect on tight junction permeability without pore-forming claudins.
  • Claudin-4 selectively inhibited flux through cation channels formed by claudins 2 or 15.
  • Claudin-4 disrupted higher-order structures and channels formed by other claudins, leading to their endocytosis.
  • Claudin-4 is incapable of independent polymerization.

Conclusions:

  • Claudin-4 regulates paracellular permeability through interclaudin interference.
  • This mechanism involves disrupting the structure and function of pore-forming claudins.
  • Interclaudin interference represents a novel mechanism for tight junction barrier regulation.