scholarly journals Continuous endocytic recycling of tight junction proteins: how and why?

2012 ◽  
Vol 53 ◽  
pp. 41-54 ◽  
Author(s):  
Andrew D. Chalmers ◽  
Paul Whitley
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
Dynamic Behaviour ◽  
Tight Junction Proteins ◽  
Tissue Remodelling ◽  
Extracellular Signals ◽  
Junctional Proteins ◽  
Cytoplasmic Proteins ◽  
Dynamic Structures ◽  
Junction Proteins

Tight junctions consist of many proteins, including transmembrane and associated cytoplasmic proteins, which act to provide a barrier regulating transport across epithelial and endothelial tissues. These junctions are dynamic structures that are able to maintain barrier function during tissue remodelling and rapidly alter it in response to extracellular signals. Individual components of tight junctions also show dynamic behaviour, including migration within the junction and exchange in and out of the junctions. In addition, it is becoming clear that some tight junction proteins undergo continuous endocytosis and recycling back to the plasma membrane. Regulation of endocytic trafficking of junctional proteins may provide a way of rapidly remodelling junctions and will be the focus of this chapter.

scholarly journals A novel in vitro platform for the study of SN38-induced mucosal damage and the development of Toll-like receptor 4-targeted therapeutic options

2016 ◽  
Vol 241 (13) ◽  
pp. 1386-1394 ◽  
Author(s):  
Hannah R Wardill ◽  
Rachel J Gibson ◽  
Ysabella ZA Van Sebille ◽  
Kate R Secombe ◽  
Richard M Logan ◽  
...  
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
Mucosal Damage ◽  
Toll Like Receptor ◽  
Tight Junction Proteins ◽  
T84 Cells ◽  
Toll Like Receptor 4 ◽  
Transmission Electron ◽  
Junction Proteins

Tight junction and epithelial barrier disruption is a common trait of many gastrointestinal pathologies, including chemotherapy-induced gut toxicity. Currently, there are no validated in vitro models suitable for the study of chemotherapy-induced mucosal damage that allow paralleled functional and structural analyses of tight junction integrity. We therefore aimed to determine if a transparent, polyester membrane insert supports a polarized T84 monolayer with the phenotypically normal tight junctions. T84 cells (passage 5–15) were seeded into either 0.6 cm2, 0.4 µm pore mixed-cellulose transwell hanging inserts or 1.12 cm2, 0.4 µm pore polyester transwell inserts at varying densities. Transepithelial electrical resistance was measured daily to assess barrier formation. Immunofluoresence for key tight junction proteins (occludin, zonular occludens-1, claudin-1) and transmission electron microscopy were performed to assess tight junction integrity, organelle distribution, and polarity. Reverse transcription-polymerase chain reaction was performed to determine expression of toll-like receptor 4 (TLR4). Liquid chromatography was also conducted to assess SN38 degradation in this model. Polyester membrane inserts support a polarized T84 phenotype with functional tight junctions in vitro. Transmission electron microscopy indicated polarity, with apico-laterally located tight junctions. Immunofluorescence showed membranous staining for all tight junction proteins. No internalization was evident. T84 cells expressed TLR4, although this was significantly lower than levels seen in HT29 cells ( P = .0377). SN38 underwent more rapid degradation in the presence of cells (−76.04 ± 1.86%) compared to blank membrane (−48.39 ± 4.01%), indicating metabolic processes. Polyester membrane inserts provide a novel platform for paralleled functional and structural analysis of tight junction integrity in T84 monolayers. T84 cells exhibit the unique ability to metabolize SN38 as well as expressing TLR4, making this an excellent platform to study clinically relevant therapeutic interventions for SN38-induced mucosal damage by targeting TLR4.

scholarly journals Structural Features of Tight-Junction Proteins

2019 ◽  
Vol 20 (23) ◽  
pp. 6020 ◽  
Author(s):  
Udo Heinemann ◽  
Anja Schuetz
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
Protein Interactions ◽  
Three Dimensional ◽  
Structural Features ◽  
Resonance Spectroscopy ◽  
Tight Junction Proteins ◽  
Protein Protein Interactions ◽  
X Ray Crystallography ◽  
Junction Proteins

Tight junctions are complex supramolecular entities composed of integral membrane proteins, membrane-associated and soluble cytoplasmic proteins engaging in an intricate and dynamic system of protein–protein interactions. Three-dimensional structures of several tight-junction proteins or their isolated domains have been determined by X-ray crystallography, nuclear magnetic resonance spectroscopy, and cryo-electron microscopy. These structures provide direct insight into molecular interactions that contribute to the formation, integrity, or function of tight junctions. In addition, the known experimental structures have allowed the modeling of ligand-binding events involving tight-junction proteins. Here, we review the published structures of tight-junction proteins. We show that these proteins are composed of a limited set of structural motifs and highlight common types of interactions between tight-junction proteins and their ligands involving these motifs.

Biomarkers of intestinal barrier function in multiple sclerosis are associated with disease activity

2019 ◽  
Vol 26 (11) ◽  
pp. 1340-1350 ◽  
Author(s):  
Carlos R Camara-Lemarroy ◽  
Claudia Silva ◽  
Jamie Greenfield ◽  
Wei-Qiao Liu ◽  
Luanne M Metz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Tight Junction ◽  
Disease Progression ◽  
Tight Junctions ◽  
Binding Protein ◽  
Intestinal Barrier ◽  
Tight Junction Proteins ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Junction Proteins

Background: Recent evidence suggests a role for the gut–brain axis in the pathophysiology of multiple sclerosis (MS). Materials and methods: We studied biomarkers of intestinal permeability in 126 people with MS (57 relapsing-remitting multiple sclerosis (RRMS) and 69 progressive MS) and in a group of healthy controls for comparison. Serum/plasma concentrations of zonulin (a regulator of enterocyte tight junctions), tight junction proteins (ZO-1 and occludin), intestinal fatty acid binding protein (IFABP)/ileal bile acid binding protein (IBABP), D-lactate, and lipopolysaccharide (LPS) binding protein were measured. Results: Zonulin concentrations were significantly higher when a concurrent magnetic resonance imaging (MRI) confirmed the presence of blood–brain barrier (BBB) disruption (Gad+ RRMS) and were correlated with tight junction proteins. IBABP and D-lactate were elevated in people with RRMS compared to controls, but did not discriminate between Gad+ and Gad– subgroups. Baseline zonulin concentrations were associated with 1-year disease progression in progressive MS. Conclusions: People with MS have altered biomarkers of intestinal barrier integrity. Zonulin concentrations are associated with 1-year disease progression in progressive MS and closely mirror BBB breakdown in RRMS. Zonulin may mediate breakdown of both the intestinal barrier and the BBB in gut dysbiosis through the regulation of tight junctions. This could explain how the gut–brain axis modulates neuroinflammation in MS.

Distribution of the tight junction proteins ZO-1, occludin, and claudin-4, -8, and -12 in bladder epithelium

2004 ◽  
Vol 287 (2) ◽  
pp. F305-F318 ◽  
Author(s):  
Prasad Acharya ◽  
Jonathan Beckel ◽  
Wily G. Ruiz ◽  
Edward Wang ◽  
Raul Rojas ◽  
...  
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
High Resistance ◽  
Cell Contact ◽  
Tight Junction Proteins ◽  
Bladder Epithelium ◽  
Cell Layers ◽  
Umbrella Cells ◽  
Junction Proteins ◽  
Cell Cell

In mammals, the bladder stores urine without permitting the passage of urine contents into the bloodstream, a function, in part, of the uroepithelial-associated tight junction complex. The protein constituents that make up this high-resistance barrier in the bladder are currently unknown, although the claudins, a multigene family, are thought to govern paracellular transport in other epithelia. Reverse transcriptase-polymerase chain reaction analysis was used to define that mRNA for claudin-2, -4, -8, -12, and -13 was expressed in mouse bladder tissue. The localization of these claudins, as well as the tight junction-associated proteins zonula occludens-1 (ZO-1) and occludin, within the bladder epithelium was determined by immunofluorescence microscopy. As expected, occludin and ZO-1 were localized to the tight junctions of rat, mouse, and rabbit umbrella cells. Intriguingly, ZO-1 in mouse epithelium, ZO-1 in the dome region of rabbit bladders and occludin in rat and mouse bladders were also expressed in the underlying intermediate and basal cell layers. Claudin-4, -8, and -12 were found in the umbrella cell tight junction; however, additional staining of claudin-4 was observed along the sites of cell-cell contact in the underlying cell layers of rat, mouse, and rabbit tissue. No claudin-2 staining was associated with tight junctions in the uroepithelium. Our results indicate that claudin-4, -8, and -12 are expressed in umbrella cells, where they may impart the high-resistance phenotype associated with this cell type, and that in some instances tight junction proteins are also associated at the sites of cell contact of the underlying cell layers, perhaps playing some role in cell-cell adhesion.

Tight junction proteins in HCC and metastatic liver tumours

2005 ◽  
Vol 43 (05) ◽  
Author(s):  
Cs Páska ◽  
E Orbán ◽  
A Kiss ◽  
Zs Schaff ◽  
A Szijjártó ◽  
...  
Keyword(s):  
Tight Junction ◽  
Tight Junction Proteins ◽  
Liver Tumours ◽  
Metastatic Liver ◽  
Junction Proteins

Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle

2017 ◽  
Vol 95 (3) ◽  
pp. 1313 ◽  
Author(s):  
L. Zhang ◽  
L. F. Schütz ◽  
C. L. Robinson ◽  
M. L. Totty ◽  
L. J. Spicer
Keyword(s):  
Gene Expression ◽  
Tight Junction ◽  
Tight Junction Proteins ◽  
Junction Proteins
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