PreprintCited by 1,059Barrier Structure and Function StudiesIon Transport and Channel RegulationCell Adhesion Molecules Research

Physiology and function of the tight junction

Open access
Anderson, J. M., Van Itallie, C. M.·2009·Cold Spring Harbor Perspectives in Biology

Abstract

Understanding of tight junctions has evolved from their historical perception as inert solute barriers to recognition of their physiological and biochemical complexity. Many proteins are specifically localized to tight junctions, including cytoplasmic actin-binding proteins and adhesive transmembrane proteins. Among the latter are claudins, which are critical barrier proteins. Current information suggests that the paracellular barrier is most usefully modeled as having two physiologic components: a system of charge-selective small pores, 4 A in radius, and a second pathway created by larger discontinuities in the barrier, lacking charge or size discrimination. The first pathway is influenced by claudin expression patterns and the second is likely controlled by different proteins and signals. Recent information on claudin function and disease-causing mutations have led to a more complete understanding of their role in barrier formation, but progress is impeded by lack of high resolution structural information.

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Crossref · 10.1101/cshperspect.a002584

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  • Tight junctions are the main functional components in sustaining the permeability barrier and controlling tissue homeostasis in the blood-brain barrier.

    “In the BBB, tight junctions are the main functional components in sustaining the permeability barrier and controlling tissue homeostasis.88–91”

    From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [89]

    The Abstract (page unavailable) describes tight junctions as barriers that separate tissue spaces and regulate solute movement. The Size section (page unavailable) reports that deleting claudin-5 increases tight-junction permeability in blood vessels. These passages support a permeability-barrier role, but do not establish that tight junctions are the main functional components of the blood-brain barrier or that they control its tissue homeostasis. (LLM, conf=0.84)

    Experimental — accuracy not yet measured
  • Solutes and water cross tight junctions through 2 distinct pathways based on their size and charge selectivity: the pore pathway and the leak pathway.

    “It was reported that solutes and water cross TJs through 2 distinct pathways based on their size and charge selectivity: the pore pathway48, 49, 50 and the leak pathway.48,51”

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Authors
Anderson, J. M., & Van Itallie, C. M.
Affiliations
University of North Carolina at Chapel Hill (US)
Venue
Cold Spring Harbor Perspectives in Biology
Published
2009-08-01
Volume
1
Issue
2
Pages
a002584-a002584
ISSN
1943-0264 (ISSN-L)
OpenAlex
W4297977229
Cited by
1,059
References
121
Citations by year
2026: 44 · 2025: 61 · 2024: 75 · 2023: 64 · 2022: 72 · 2021: 88 · 2020: 91 · 2019: 78 · 2018: 62 · 2017: 69 · 2016: 56 · 2015: 66 · 2014: 60 · 2013: 63 · 2012: 56
Type
posted content
Language
en
Open access
Locations
  • Cold Spring Harbor Perspectives in Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • National Institutes of Health (DK034987, DK61397)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK45134, R01DK045134, DK61397, R56DK061397, R01DK061397, P30DK034987)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
tight junctions, paracellular barrier, claudins, tight junction proteins, barrier permeability, actin-binding proteins
MeSH terms
Amino Acid Sequence, Animals, Biological Transport, Cell Membrane, Cytoplasm, Electrophysiology, Humans, Models, Biological, Molecular Sequence Data, Sequence Homology, Amino Acid, Tight Junctions, Genetic Predisposition to Disease, Claudins

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