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Tight junctions contain oligomeric protein assembly critical for maintaining blood-brain barrier integrity in vivo.
J Neurochem. 2007 Dec; 103(6):2540-55.JN

Abstract

Tight junctions (TJs) are major components of the blood-brain barrier (BBB) that physically obstruct the interendothelial space and restrict paracellular diffusion of blood-borne substances from the peripheral circulation to the CNS. TJs are dynamic structures whose intricate arrangement of oligomeric transmembrane and accessory proteins rapidly alters in response to external stressors to produce changes in BBB permeability. In this study, we investigate the constitutive trafficking of the TJ transmembrane proteins occludin and claudin-5 that are essential for forming the TJ seal between microvascular endothelial cells that inhibits paracellular diffusion. Using a novel, detergent-free OptiPrep density-gradient method to fractionate rat cerebral microvessels, we identify a plasma membrane lipid raft domain that contains oligomeric occludin and claudin-5. Our data suggest that oligomerization of occludin involves disulfide bond formation within transmembrane regions, and that assembly of the TJ oligomeric protein complex is facilitated by an oligomeric caveolin scaffold. This is the first time that distribution of oligomeric TJ transmembrane proteins within plasma membrane lipid rafts at the BBB has been examined in vivo. The findings reported in this study are critical to understand the mechanism of assembly of the TJ multiprotein complex that is essential for maintaining BBB integrity.

Authors+Show Affiliations

Department of Medical Pharmacology, University of Arizona College of Medicine, 1501 N. Campbell Ave, Tucson, Arizona, USA. gwenm@email.arizona.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17931362

Citation

McCaffrey, Gwen, et al. "Tight Junctions Contain Oligomeric Protein Assembly Critical for Maintaining Blood-brain Barrier Integrity in Vivo." Journal of Neurochemistry, vol. 103, no. 6, 2007, pp. 2540-55.
McCaffrey G, Staatz WD, Quigley CA, et al. Tight junctions contain oligomeric protein assembly critical for maintaining blood-brain barrier integrity in vivo. J Neurochem. 2007;103(6):2540-55.
McCaffrey, G., Staatz, W. D., Quigley, C. A., Nametz, N., Seelbach, M. J., Campos, C. R., Brooks, T. A., Egleton, R. D., & Davis, T. P. (2007). Tight junctions contain oligomeric protein assembly critical for maintaining blood-brain barrier integrity in vivo. Journal of Neurochemistry, 103(6), 2540-55. https://doi.org/10.1111/j.1471-4159.2007.04943.x
McCaffrey G, et al. Tight Junctions Contain Oligomeric Protein Assembly Critical for Maintaining Blood-brain Barrier Integrity in Vivo. J Neurochem. 2007;103(6):2540-55. PubMed PMID: 17931362.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tight junctions contain oligomeric protein assembly critical for maintaining blood-brain barrier integrity in vivo. AU - McCaffrey,Gwen, AU - Staatz,William D, AU - Quigley,Carolyn A, AU - Nametz,Nicole, AU - Seelbach,Melissa J, AU - Campos,Chris R, AU - Brooks,Tracy A, AU - Egleton,Richard D, AU - Davis,Thomas P, PY - 2007/10/13/pubmed PY - 2011/7/20/medline PY - 2007/10/13/entrez SP - 2540 EP - 55 JF - Journal of neurochemistry JO - J. Neurochem. VL - 103 IS - 6 N2 - Tight junctions (TJs) are major components of the blood-brain barrier (BBB) that physically obstruct the interendothelial space and restrict paracellular diffusion of blood-borne substances from the peripheral circulation to the CNS. TJs are dynamic structures whose intricate arrangement of oligomeric transmembrane and accessory proteins rapidly alters in response to external stressors to produce changes in BBB permeability. In this study, we investigate the constitutive trafficking of the TJ transmembrane proteins occludin and claudin-5 that are essential for forming the TJ seal between microvascular endothelial cells that inhibits paracellular diffusion. Using a novel, detergent-free OptiPrep density-gradient method to fractionate rat cerebral microvessels, we identify a plasma membrane lipid raft domain that contains oligomeric occludin and claudin-5. Our data suggest that oligomerization of occludin involves disulfide bond formation within transmembrane regions, and that assembly of the TJ oligomeric protein complex is facilitated by an oligomeric caveolin scaffold. This is the first time that distribution of oligomeric TJ transmembrane proteins within plasma membrane lipid rafts at the BBB has been examined in vivo. The findings reported in this study are critical to understand the mechanism of assembly of the TJ multiprotein complex that is essential for maintaining BBB integrity. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/17931362/Tight_junctions_contain_oligomeric_protein_assembly_critical_for_maintaining_blood_brain_barrier_integrity_in_vivo_ L2 - https://doi.org/10.1111/j.1471-4159.2007.04943.x DB - PRIME DP - Unbound Medicine ER -