Brain barriers: Crosstalk between complex tight junctions and adherens junctions
Open accessAbstract
Unique intercellular junctional complexes between the central nervous system (CNS) microvascular endothelial cells and the choroid plexus epithelial cells form the endothelial blood–brain barrier (BBB) and the epithelial blood–cerebrospinal fluid barrier (BCSFB), respectively. These barriers inhibit paracellular diffusion, thereby protecting the CNS from fluctuations in the blood. Studies of brain barrier integrity during development, normal physiology, and disease have focused on BBB and BCSFB tight junctions but not the corresponding endothelial and epithelial adherens junctions. The crosstalk between adherens junctions and tight junctions in maintaining barrier integrity is an understudied area that may represent a promising target for influencing brain barrier function.
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Adherens junction proteins VE-cadherin and PECAM-1 form homophilic endothelial-to-endothelial contacts roughly 20 nm wide.
“Closest to the basolateral membrane, AJ proteins, VE-cadherin, and platelet endothelial cell adhesion molecule-1 (PECAM-1) form homophilic endothelial-to-endothelial”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [590]
The Figure 1 caption (p. 2) says VE-cadherin forms homophilic contacts between adjacent endothelial cells. The table in “Maturation of brain barrier junctional complexes during development” (p. 5) places PECAM-1 at endothelial cell-to-cell junctions but lists it outside organized adherens and tight junctions. Our copy does not establish that PECAM-1 forms the claimed homophilic AJ contacts or that the contacts are roughly 20 nm wide. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTight junction proteins claudin-1, claudin-3, claudin-5, claudin-12, and occludin limit paracellular diffusion of solutes and ions across the blood-brain barrier.
“Closest to the apical membrane, TJ proteins claudin-1, -3, -5, and -12, and occludin limit paracellular diffusion of solutes and ions across the BBB (438, 590) (FIGURE 2) .”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [590]
The Introduction (p. 1) says BBB tight junctions prevent paracellular diffusion, and the junctional-protein table (pp. 4–5) supports a barrier role for claudin-5 and describes roles for claudin-1 and occludin. But the table says claudin-12’s function at the BBB is unknown and reports that claudin-3 seals the blood–CSF barrier, not BBB tight junctions, under neuroinflammatory conditions. It therefore does not support assigning the stated BBB diffusion-limiting role to all five proteins. (LLM, conf=0.89)
Experimental — accuracy not yet measuredEndothelial cells interact with extracellular matrix proteins in the capillary basement membrane, including collagen, perlecan, and laminin, via α- and β-integrin receptors.
“Endothelial cells interact with the extracellular matrix (ECM) proteins in the capillary basement membrane including collagen, perlecan, and laminin via 𝛂 - and 𝛃 -integrin receptors, which form transmembrane heterodimers that functionally link the ECM with the cell cytoskeleton (590).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [590]
The Figure 2 caption in “Maturation of brain barrier junctional complexes during development” (p. 8) says BBB endothelial cells are anchored by β1-integrins to laminin, collagen, and perlecan in the endothelial basement membrane. Our copy does not establish the citing sentence’s additional description of α- and β-integrin heterodimers linking the ECM to the cytoskeleton. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIntegrin receptors form transmembrane heterodimers that functionally link the extracellular matrix with the cell cytoskeleton.
“which form transmembrane heterodimers that functionally link the ECM with the cell cytoskeleton (590).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [590]
The section on maturation of brain barrier junctional complexes (p. 8) says that β1-integrins anchor endothelial cells to extracellular-matrix proteins. It does not state that integrins form transmembrane heterodimers or that they link the matrix to the cell cytoskeleton; the cytoskeletal links described elsewhere in that section concern other junctional proteins. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIn contrast to leaky capillary endothelium in peripheral organs, the BBB endothelium is sealed by TJs and has a low rate of bulk-flow transcytosis.
“In contrast to leaky capillary endothelium in peripheral organs (391), the BBB endothelium is sealed by TJs (492, 590, 682) and has low rate of bulk-flow transcytosis (538, 682).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [590]
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- Authors
- Tietz, S., & Engelhardt, B.
- Affiliations
- University of Bern (CH)
- Corresponding author
- Engelhardt, Britta
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2015-05-25
- Volume
- 209
- Issue
- 4
- Pages
- 493-506
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC4442813
- OpenAlex
- W1929386789
- Cited by
- 551
- References
- 140
- Citations by year
- 2026: 44 · 2025: 43 · 2024: 44 · 2023: 56 · 2022: 65 · 2021: 65 · 2020: 63 · 2019: 49 · 2018: 43 · 2017: 47 · 2016: 26 · 2015: 6
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion, cc-by-nc-sa)
- Open Access CRIS of the University of Bern
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- blood-brain barrier, blood-CSF barrier, tight junctions, adherens junctions, endothelial cells, choroid plexus epithelial cells, paracellular diffusion, barrier integrity
- MeSH terms
- Animals, Biological Transport, Blood-Brain Barrier, Brain, Endothelium, Vascular, Humans, Tight Junctions, Adherens Junctions, Endothelial Cells, Microvessels
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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