The tight junction: Structure and function

Hirsch, M.; Noske, W

doi:10.1016/0968-4328(93)90057-8

Cited by 25 publications

(11 citation statements)

References 314 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TJs observed in freeze-fracture replica of cocultures displayed similar structures and organization to those described in in vitro BBB models (16,(52)(53)(54). Moreover, in our cocultures, TJs exhibit the morphological appearance found in brain microvessels with strands forming complex networks (55,56).…”

Section: Discussionmentioning

confidence: 48%

Anin vitroblood–brain barrier model: Cocultures between endothelial cells and organotypic brain slice cultures

Duport¹,

Robert²,

Michelet³

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

This communication describes a novel in vitro blood-brain barrier (BBB) model: organotypic slice cultures from the central nervous system were overlaid on endothelial cell monolayers grown on permeable membranes. Morphological, electrophysiological, and microdialysis approaches were carried out to characterize and validate this model. After 10 days in coculture, morphological studies reveal the presence of tight junctions. Electrophysiological recordings of neuronal activity performed on organotypic cultures with or without an endothelial cell monolayer show that amplitude of evoked responses were comparable, indicating good viability of cocultures after 2 weeks. Perfusion of known BBB permeable or nonpermeable molecules was used to test the coculture tightness in conjunction with electrophysiological or microdialysis approaches: application of glutamate (Glu), which doesn't easily cross the BBB, triggers off rhythmic activity only in control cultures, whereas epileptogenic activity was observed in both control cultures and cocultures during perfusions with picrotoxin, a molecule that can diffuse through the BBB. Finally, the microdialysis technique was used to determine the permeability of molecules coming from the perfusion chamber: L-dopa, dopamine, and Glu were employed to assess the selective permeability of the coculture model. Thus, these results indicate that the in vitro model described possesses characteristics similar to those of the BBB in situ and that cocultures of organotypic slices and endothelial cell monolayers have potential as a powerful tool for studying biochemical mechanisms regulating BBB function and drug delivery to the central nervous system.The microenvironment of the central nervous system (CNS) is important for neuronal function. In this context, the bloodbrain barrier (BBB) provides and maintains the extracellular medium compatible with normal neuronal activity. Through multiple studies, the characteristics of the BBB in mammals were found to be due to cerebral endothelial cells. Among these characteristics, the presence of tight junctions (TJs), the selective permeability, and the polarity were found to be essential for a functional BBB (1-3).The difficulties inherent to the use of whole animals as experimental models for studying permeability and metabolic processes at the cellular level has led to major efforts in the last decades to design suitable in vitro models. Three prototypes are noteworthy: the first consists of suspensions of isolated microvessels obtained from cerebral cortex gray matter (4-7). The second was developed following the demonstration by Panula et al. (8) that brain endothelial cells could be maintained in culture. In this model, primary passage cultures and clones (9, 10) of isolated brain endothelial cells were used as an in vitro BBB (11-13). The third was provided by the work of Stewart and Willey (14) and Janzer and Raff (15) on the importance of the cellular environment of endothelial cells. As a consequence, it has been possible to simulate a...

show abstract

Section: Discussionmentioning

confidence: 48%

Anin vitroblood–brain barrier model: Cocultures between endothelial cells and organotypic brain slice cultures

Duport¹,

Robert²,

Michelet³

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…This impaired structural relationship may in turn affect functional properties of tight junctions. In our previous study, Ca ++ , Mg ++ -ATPase, a membranebound ectoenzyme, was found to be redistributed from the bile canalicular membrane to the entire plasma mem- brane of hepatocytes after 7 days of CBDL (Song et al 1996), which may reflect disturbed functioning of tight junctions as barriers to maintain the polarity of plasma membrane proteins Gumbiner 1987;Hirsch and Noske 1993). Double-labeling of F-actin and ZO-1 allowed us to study the exact distribution pattern of protein ZO-1 over the different plasma membrane domains of hepatocytes.…”

Section: Discussionmentioning

confidence: 97%

Disturbed structural interactions between microfilaments and tight junctions in rat hepatocytes during extrahepatic cholestasis induced by common bile duct ligation

Song

Marle

Noorden

et al. 1996

Histochem Cell Biol

View full text Add to dashboard Cite

Microfilaments in epithelial cells are important for the structural and functional integrity of tight junctions. In the present study, we examined the relationship between microfilaments and tight junctions in hepatocytes of rat liver following common bile duct ligation (CBDL) for up to 2 weeks. Actin filaments and tight junctions were studied by fluorescence microscopy using 7-nitrobenzene-2-oxa-1,3-diazole phallacidin (NBD-ph) and an anti-ZO-1 antibody, respectively. Double-stained sections were examined with confocal laser scanning microscopy (CLSM). Electron microscopy was applied for the assessment of structural alterations in microfilaments and in tight junctions with detergent-extraction and freeze-fracture preparations. Our results showed that F-actin was present at the entire plasma membrane of hepatocytes in control liver, whereas CBDL increased the amount of F-actin mainly at the bile canalicular and lateral plasma membranes. Simultaneously, the immunofluorescence of ZO-1 underwent striking changes, i.e., from a uniform to an irregular staining pattern with various fluorescence intensities. CLSM demonstrated a colocalization of ZO-1 and F-actin in control liver and its deterioration in CBDL liver. Electron microscopy showed marked alterations of microfilaments and tight junctions due to CBDL. It is concluded that actin filaments are intimately associated with tight junctions in normal hepatocytes. CBDL impairs this association by progressively diminishing the structural interaction between F-actin and ZO-1, which may in turn lead to functional disturbances of tight junctions.

show abstract

“…T HE tight junction (zonula occludens) is a fundamental type of intercellular junction that occurs in polarized epithelia and certain endothelia and is believed to provide a permeability barrier to prevent paracellular transport of molecules and particles and to restrict the lateral diffusion of membrane lipids and proteins (for reviews see Pinto da Silva and Kachar, 1982;Madara, 1988;Simons, 1990;Citi, 1993;Gumbiner, 1993;Hirsch and Noske, 1993). Ultrastructurally, tight junctions represent a system of linear close contacts between the two plasma membranes which on freeze-fractures along the hydrophobic plane appear as a network of anastomizing strands.…”

mentioning

confidence: 99%

Symplekin, a novel type of tight junction plaque protein.

Keon

Schäfer

Kühn

et al. 1996

The Journal of Cell Biology

280

173

View full text Add to dashboard Cite

Abstract. Using a monoclonal antibody we have identified and cDNA-cloned a novel type of protein localized, by light and electron microscopy, to the plaque associated with the cytoplasmic face of the tight junction-containing zone (zonula occludens) of polar epithelial cells and of Sertoli cells of testis, but absent from the junctions of vascular endothelia. The ~3.7-kb mRNA encodes a polypeptide of 1142 amino acids (calculated molecular weight 126.5 kD, pI 6.25), for which the name "symplekin" (from Greek cyag~tn~.~ new, to tie together, to weave, to be intertwined) is proposed. However, both the mRNA and the protein can also be detected in a wide range of cell types that do not form tight junctions or are even completely devoid of any stable cell contacts. Careful analyses have revealed that the protein occurs in all these diverse cells in the nucleoplasm, and only in those ceils forming tight junctions is it recruited, partly but specifically, to the plaque structure of the zonula occludens. We discuss symplekin as a representative of a group of dual residence proteins which occur and probably function in the nucleus as well as in the plaques exclusive for either tight junctions, adherens junctions, or desmosomes.

show abstract

The tight junction: Structure and function

Cited by 25 publications

References 314 publications

Anin vitroblood–brain barrier model: Cocultures between endothelial cells and organotypic brain slice cultures

Anin vitroblood–brain barrier model: Cocultures between endothelial cells and organotypic brain slice cultures

Disturbed structural interactions between microfilaments and tight junctions in rat hepatocytes during extrahepatic cholestasis induced by common bile duct ligation

Symplekin, a novel type of tight junction plaque protein.

Contact Info

Product

Resources

About