Structure, biochemistry, and assembly of epithelial tight junctions
Abstract
The zonula occludens (ZO), also referred to as the tight junction, forms the barrier to the diffusion of molecules and ions across the epithelial cell layer through the paracellular space. The level of electrical resistance of the paracellular pathway seems to depend on the number of strands in the ZO observed by freeze-fracture electron microscopy (EM). The ZO also forms the boundary between the compositionally distinct apical and basolateral plasma membrane domains because it is a barrier to the lateral diffusion of lipids and membrane proteins that reside in the extracytoplasmic leaflet of the membrane bilayer. In contrast to its appearance in transmission EM, the tight junction is not a fusion between the outer membrane leaflets of neighboring cells. Rather it consists of protein molecules, including the newly discovered protein ZO-1 and probably others, which bring the plasma membranes into extremely close apposition so as to occlude the extracellular space. Very little is known about the assembly of tight junctions, but several kinds of evidence suggest that they are very dynamic structures. Other elements of the epithelial junctional complex including the zonula adherens (ZA), the Ca2+-dependent cell adhesion molecule uvomorulin, or L-CAM, and actin filaments of the cytoskeleton may participate in the assembly of the ZO.
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Tight junctions restrict the crossing of hydrophilic molecules and macromolecules.
“They are also known as occluding junctions or zonulae occludes which can restrict the cross of hydrophilic molecules and macromolecules.92”
From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [92]
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- Authors
- Gumbiner, B.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Gumbiner, B.
- ORCID
- Gumbiner, B.
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 1987-12-01
- Volume
- 253
- Issue
- 6
- Pages
- C749-C758
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2177243316
- Cited by
- 531
- References
- 0
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 9 · 2016: 10 · 2015: 6 · 2014: 10 · 2013: 1 · 2012: 4
- FWCI
- 16.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2s07rr005355-30)
- National Center for Research Resources (S07 RR-05355)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- tight junctions, zonula occludens, ZO-1, paracellular barrier, epithelial permeability, tight junction assembly, adherens junctions, uvomorulin, actin cytoskeleton, cell adhesion
- MeSH terms
- Animals, Cell Adhesion, Cell Compartmentation, Cell Membrane, Epithelium, Humans, Intercellular Junctions, Permeability
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