Tight junctions, tight junction proteins and paracellular permeability across the gill epithelium of fishes: A review

2012 ◽  
Vol 184 (3) ◽  
pp. 269-281 ◽  
Author(s):  
Helen Chasiotis ◽  
Dennis Kolosov ◽  
Phuong Bui ◽  
Scott P. Kelly
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
Paracellular Permeability ◽  
Gill Epithelium ◽  
Tight Junction Proteins ◽  
Junction Proteins

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.

Vasoactive intestinal peptide ameliorates intestinal barrier disruption associated withCitrobacter rodentium-induced colitis

2009 ◽  
Vol 297 (4) ◽  
pp. G735-G750 ◽  
Author(s):  
V. S. Conlin ◽  
X. Wu ◽  
C. Nguyen ◽  
C. Dai ◽  
B. A. Vallance ◽  
...  
Keyword(s):  
Tight Junction ◽  
Myosin Light Chain ◽  
Intestinal Barrier ◽  
Paracellular Permeability ◽  
Epithelial Barrier ◽  
Tight Junction Proteins ◽  
Epithelial Barrier Function ◽  
Junction Proteins

Attaching and effacing bacterial pathogens attach to the apical surface of epithelial cells and disrupt epithelial barrier function, increasing permeability and allowing luminal contents access to the underlying milieu. Previous in vitro studies demonstrated that the neuropeptide vasoactive intestinal peptide (VIP) regulates epithelial paracellular permeability, and the high concentrations and close proximity of VIP-containing nerve fibers to intestinal epithelial cells would support such a function in vivo. The aim of this study was to examine whether VIP treatment modulated Citrobacter rodentium-induced disruption of intestinal barrier integrity and to identify potential mechanisms of action. Administration of VIP had no effect on bacterial attachment although histopathological scoring demonstrated a VIP-induced amelioration of colitis-induced epithelial damage compared with controls. VIP treatment prevented the infection-induced increase in mannitol flux a measure of paracellular permeability, resulting in levels similar to control mice, and immunohistochemical studies demonstrated that VIP prevented the translocation of tight junction proteins: zonula occludens-1, occludin, and claudin-3. Enteropathogenic Escherichia coli (EPEC) infection of Caco-2 monolayers confirmed a protective role for VIP on epithelial barrier function. VIP prevented EPEC-induced increase in long myosin light chain kinase (MLCK) expression and myosin light chain phosphorylation (p-MLC). Furthermore, MLCK inhibition significantly attenuated bacterial-induced epithelial damage both in vivo and in vitro. In conclusion, our results indicate that VIP protects the colonic epithelial barrier by minimizing bacterial-induced redistribution of tight junction proteins in part through actions on MLCK and MLC phosphorylation.

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.

scholarly journals Cyclic stretch disrupts apical junctional complexes in Caco-2 cell monolayers by a JNK-2-, c-Src-, and MLCK-dependent mechanism

2014 ◽  
Vol 306 (11) ◽  
pp. G947-G958 ◽  
Author(s):  
Geetha Samak ◽  
Ruchika Gangwar ◽  
Lynn M. Crosby ◽  
Leena P. Desai ◽  
Kristina Wilhelm ◽  
...  
Keyword(s):  
Tight Junction ◽  
Actin Cytoskeleton ◽  
Tight Junctions ◽  
Src Kinase ◽  
Adherens Junction ◽  
Paracellular Permeability ◽  
Cyclic Stretch ◽  
Cell Monolayers ◽  
Dependent Mechanism ◽  
Junction Proteins

The intestinal epithelium is subjected to various types of mechanical stress. In this study, we investigated the impact of cyclic stretch on tight junction and adherens junction integrity in Caco-2 cell monolayers. Stretch for 2 h resulted in a dramatic modulation of tight junction protein distribution from a linear organization into wavy structure. Continuation of cyclic stretch for 6 h led to redistribution of tight junction proteins from the intercellular junctions into the intracellular compartment. Disruption of tight junctions was associated with redistribution of adherens junction proteins, E-cadherin and β-catenin, and dissociation of the actin cytoskeleton at the actomyosin belt. Stretch activates JNK2, c-Src, and myosin light-chain kinase (MLCK). Inhibition of JNK, Src kinase or MLCK activity and knockdown of JNK2 or c-Src attenuated stretch-induced disruption of tight junctions, adherens junctions, and actin cytoskeleton. Paracellular permeability measured by a novel method demonstrated that cyclic stretch increases paracellular permeability by a JNK, Src kinase, and MLCK-dependent mechanism. Stretch increased tyrosine phosphorylation of occludin, ZO-1, E-cadherin, and β-catenin. Inhibition of JNK or Src kinase attenuated stretch-induced occludin phosphorylation. Immunofluorescence localization indicated that phospho-MLC colocalizes with the vesicle-like actin structure at the actomyosin belt in stretched cells. On the other hand, phospho-c-Src colocalizes with the actin at the apical region of cells. This study demonstrates that cyclic stretch disrupts tight junctions and adherens junctions by a JNK2, c-Src, and MLCK-dependent mechanism.

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.

Sign in / Sign up

Export Citation Format

Share Document