Brain Barriers: Crosstalk Between Complex Tight Junctions and Adherens Junctions

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2015 May 27

PMID 26008742

Citations 255

Authors

Silvia Tietz

Britta Engelhardt

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The interaction between dysfunction of vasculature and tauopathy in Alzheimer's disease and related dementias.

Huang C, Wei Z, Zheng N, Yan J, Zhang J, Ye X Alzheimers Dement. 2025; 21(2):e14618.

PMID: 39998958 PMC: 11854360. DOI: 10.1002/alz.14618.

Deciphering the Blood-Brain Barrier Paradox in Brain Metastasis Development and Therapy.

Peters J, Teng C, Peng K, Li X Cancers (Basel). 2025; 17(2).

PMID: 39858080 PMC: 11764143. DOI: 10.3390/cancers17020298.

Vascular FLRT2 regulates venous-mediated angiogenic expansion and CNS barriergenesis.

Llao-Cid C, Peguera B, Kobialka P, Decker L, Vogenstahl J, Alivodej N Nat Commun. 2024; 15(1):10372.

PMID: 39609404 PMC: 11604978. DOI: 10.1038/s41467-024-54570-x.

Mechanisms of ozone-induced neurotoxicity in the development and progression of dementia: a brief review.

Marin-Castaneda L, Gonzalez-Garibay G, Garcia-Quintana I, Pacheco-Aispuro G, Rubio C Front Aging Neurosci. 2024; 16:1494356.

PMID: 39529750 PMC: 11552306. DOI: 10.3389/fnagi.2024.1494356.

Challenges and advances in glioblastoma targeted therapy: the promise of drug repurposing and biomarker exploration.

Bae W, Maraka S, Daher A Front Oncol. 2024; 14:1441460.

PMID: 39439947 PMC: 11493774. DOI: 10.3389/fonc.2024.1441460.

References

Strazielle N, Ghersi-Egea J . Demonstration of a coupled metabolism-efflux process at the choroid plexus as a mechanism of brain protection toward xenobiotics. J Neurosci. 1999; 19(15):6275-89. PMC: 6782833. View

Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y . Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol. 2002; 156(6):1099-111. PMC: 2173463. DOI: 10.1083/jcb.200110122. View

Huntley M, Bien-Ly N, Daneman R, Watts R . Dissecting gene expression at the blood-brain barrier. Front Neurosci. 2014; 8:355. PMC: 4222230. DOI: 10.3389/fnins.2014.00355. View

Harris T . Adherens junction assembly and function in the Drosophila embryo. Int Rev Cell Mol Biol. 2012; 293:45-83. DOI: 10.1016/B978-0-12-394304-0.00007-5. View

Tam S, Richmond D, Kaminker J, Modrusan Z, Martin-McNulty B, Cao T . Death receptors DR6 and TROY regulate brain vascular development. Dev Cell. 2012; 22(2):403-17. DOI: 10.1016/j.devcel.2011.11.018. View

Wessel F, Winderlich M, Holm M, Frye M, Rivera-Galdos R, Vockel M . Leukocyte extravasation and vascular permeability are each controlled in vivo by different tyrosine residues of VE-cadherin. Nat Immunol. 2014; 15(3):223-30. DOI: 10.1038/ni.2824. View

Giannotta M, Trani M, Dejana E . VE-cadherin and endothelial adherens junctions: active guardians of vascular integrity. Dev Cell. 2013; 26(5):441-54. DOI: 10.1016/j.devcel.2013.08.020. View

Engelhardt B, Liebner S . Novel insights into the development and maintenance of the blood-brain barrier. Cell Tissue Res. 2014; 355(3):687-99. PMC: 3972432. DOI: 10.1007/s00441-014-1811-2. View

Siegenthaler J, Sohet F, Daneman R . 'Sealing off the CNS': cellular and molecular regulation of blood-brain barriergenesis. Curr Opin Neurobiol. 2013; 23(6):1057-64. PMC: 4061913. DOI: 10.1016/j.conb.2013.06.006. View

10.

Errede M, Girolamo F, Ferrara G, Strippoli M, Morando S, Boldrin V . Blood-brain barrier alterations in the cerebral cortex in experimental autoimmune encephalomyelitis. J Neuropathol Exp Neurol. 2012; 71(10):840-54. DOI: 10.1097/NEN.0b013e31826ac110. View

11.

Bixel G, Kloep S, Butz S, Petri B, Engelhardt B, Vestweber D . Mouse CD99 participates in T-cell recruitment into inflamed skin. Blood. 2004; 104(10):3205-13. DOI: 10.1182/blood-2004-03-1184. View

12.

Engelhardt B, Wolburg-Buchholz K, Wolburg H . Involvement of the choroid plexus in central nervous system inflammation. Microsc Res Tech. 2001; 52(1):112-29. DOI: 10.1002/1097-0029(20010101)52:1<112::AID-JEMT13>3.0.CO;2-5. View

13.

Furuse M, Furuse K, Sasaki H, Tsukita S . Conversion of zonulae occludentes from tight to leaky strand type by introducing claudin-2 into Madin-Darby canine kidney I cells. J Cell Biol. 2001; 153(2):263-72. PMC: 2169456. DOI: 10.1083/jcb.153.2.263. View

14.

Murugesan N, Paul D, Lemire Y, Shrestha B, Ge S, Pachter J . Active induction of experimental autoimmune encephalomyelitis by MOG35-55 peptide immunization is associated with differential responses in separate compartments of the choroid plexus. Fluids Barriers CNS. 2012; 9(1):15. PMC: 3493354. DOI: 10.1186/2045-8118-9-15. View

15.

Liebner S, Kniesel U, Kalbacher H, Wolburg H . Correlation of tight junction morphology with the expression of tight junction proteins in blood-brain barrier endothelial cells. Eur J Cell Biol. 2000; 79(10):707-17. DOI: 10.1078/0171-9335-00101. View

16.

Kniesel U, Reichenbach A, Risau W, Wolburg H . Quantification of tight junction complexity by means of fractal analysis. Tissue Cell. 1994; 26(6):901-12. DOI: 10.1016/0040-8166(94)90039-6. View

17.

Fanning A, Jameson B, Jesaitis L, Anderson J . The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J Biol Chem. 1998; 273(45):29745-53. DOI: 10.1074/jbc.273.45.29745. View

18.

Williams D, Calderon T, Lopez L, Carvallo-Torres L, Gaskill P, Eugenin E . Mechanisms of HIV entry into the CNS: increased sensitivity of HIV infected CD14+CD16+ monocytes to CCL2 and key roles of CCR2, JAM-A, and ALCAM in diapedesis. PLoS One. 2013; 8(7):e69270. PMC: 3724935. DOI: 10.1371/journal.pone.0069270. View

19.

Figarella-Branger D, Lepidi H, Poncet C, Gambarelli D, Bianco N, Rougon G . Differential expression of cell adhesion molecules (CAM), neural CAM and epithelial cadherin in ependymomas and choroid plexus tumors. Acta Neuropathol. 1995; 89(3):248-57. DOI: 10.1007/BF00309340. View

20.

Argaw A, Gurfein B, Zhang Y, Zameer A, John G . VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown. Proc Natl Acad Sci U S A. 2009; 106(6):1977-82. PMC: 2644149. DOI: 10.1073/pnas.0808698106. View