Contribution of the tricellular tight junction to paracellular permeability in leaky and tight epithelia

2017 ◽  
Vol 1397 (1) ◽  
pp. 219-230 ◽  
Author(s):  
Susanne M. Krug
Keyword(s):  
Tight Junction ◽  
Paracellular Permeability ◽  
Tight Epithelia

Aldosterone and tight junctions: modulation of claudin-4 phosphorylation in renal collecting duct cells

2005 ◽  
Vol 289 (6) ◽  
pp. C1513-C1521 ◽  
Author(s):  
Cathy Le Moellic ◽  
Sheerazed Boulkroun ◽  
Daniel González-Nunez ◽  
Isabelle Dublineau ◽  
Francoise Cluzeaud ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Cellular Localization ◽  
Collecting Duct ◽  
Receptor Occupancy ◽  
Paracellular Permeability ◽  
Na Transport ◽  
Charge Selectivity ◽  
Tight Epithelia ◽  
Collecting Duct Cells ◽  
Renal Collecting Duct

Aldosterone classically modulates Na transport in tight epithelia such as the renal collecting duct (CD) through the transcellular route, but it is not known whether the hormone could also affect paracellular permeability. Such permeability is controlled by tight junctions (TJ) that form a size- and charge-selective barrier. Among TJ proteins, claudin-4 has been highlighted as a key element to control paracellular charge selectivity. In RCCD2 CD cells grown on filters, we have identified novel early aldosterone effects on TJ. Endogenous claudin-4 abundance and cellular localization were unaltered by aldosterone. However, the hormone promoted rapid (within 15–20 min) and transient phosphorylation of endogenous claudin-4 on threonine residues, without affecting tyrosine or serine; this event was fully developed at 10 nM aldosterone and appeared specific for aldosterone (because it is not observed after dexamethasone treatment and it depends on mineralocorticoid receptor occupancy). Within the same delay, aldosterone also promoted an increased apical-to-basal passage of 125I (a substitute for 36Cl), whereas 22Na passage was unaffected; paracellular permeability to [3H]mannitol was also reduced. Later on (45 min), a fall in transepithelial resistance was observed. These data indicate that aldosterone modulates TJ properties in renal epithelial cells.

scholarly journals Biology of claudins

2008 ◽  
Vol 295 (4) ◽  
pp. F867-F876 ◽  
Author(s):  
Susanne Angelow ◽  
Robert Ahlstrom ◽  
Alan S. L. Yu
Keyword(s):  
Tight Junction ◽  
Renal Tubule ◽  
Physiological Role ◽  
Paracellular Permeability ◽  
Normal Kidney ◽  
Tight Junction Formation ◽  
Intracellular Signals ◽  
Junction Formation ◽  
Fundamental Biology

Claudins are a family of tight junction membrane proteins that regulate paracellular permeability of epithelia, likely by forming the lining of the paracellular pore. Claudins are expressed throughout the renal tubule, and mutations in two claudin genes are now known to cause familial hypercalciuric hypomagnesemia with nephrocalcinosis. In this review, we discuss recent advances in our understanding of the physiological role of various claudins in normal kidney function, and in understanding the fundamental biology of claudins, including the molecular basis for selectivity of permeation, claudin interactions in tight junction formation, and regulation of claudins by protein kinases and other intracellular signals.

scholarly journals Clostridium difficile Toxins Disrupt Epithelial Barrier Function by Altering Membrane Microdomain Localization of Tight Junction Proteins

2001 ◽  
Vol 69 (3) ◽  
pp. 1329-1336 ◽  
Author(s):  
A. Nusrat ◽  
C. von Eichel-Streiber ◽  
J. R. Turner ◽  
P. Verkade ◽  
J. L. Madara ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Tight Junction ◽  
Pseudomembranous Colitis ◽  
Paracellular Permeability ◽  
Etiologic Agent ◽  
Membrane Microdomains ◽  
Epithelial Cell Line ◽  
Rho Proteins ◽  
Membrane Microdomain ◽  
Junction Protein

ABSTRACT The anaerobic bacterium Clostridium difficile is the etiologic agent of pseudomembranous colitis. C. difficiletoxins TcdA and TcdB are UDP-glucosyltransferases that monoglucosylate and thereby inactivate the Rho family of GTPases (W. P. Ciesla, Jr., and D. A. Bobak, J. Biol. Chem. 273:16021–16026, 1998). We utilized purified reference toxins of C. difficile, TcdA-10463 (TcdA) and TcdB-10463 (TcdB), and a model intestinal epithelial cell line to characterize their influence on tight-junction (TJ) organization and hence to analyze the mechanisms by which they contribute to the enhanced paracellular permeability and disease pathophysiology of pseudomembranous colitis. The increase in paracellular permeability induced by TcdA and TcdB was associated with disorganization of apical and basal F-actin. F-actin restructuring was paralleled by dissociation of occludin, ZO-1, and ZO-2 from the lateral TJ membrane without influencing the subjacent adherens junction protein, E-cadherin. In addition, we observed decreased association of actin with the TJ cytoplasmic plaque protein ZO-1. Differential detergent extraction and fractionation in sucrose density gradients revealed TcdB-induced redistribution of occludin and ZO-1 from detergent-insoluble fractions constituting “raft-like” membrane microdomains, suggesting an important role of Rho proteins in maintaining the association of TJ proteins with such microdomains. These toxin-mediated effects on actin and TJ structure provide a mechanism for early events in the pathophysiology of pseudomembranous colitis.

Claudins at the gate: determinants of renal epithelial tight junction paracellular permeability

2006 ◽  
Vol 290 (3) ◽  
pp. F572-F579 ◽  
Author(s):  
Daniel F. Balkovetz
Keyword(s):  
Tight Junction ◽  
Membrane Lipids ◽  
Expression Patterns ◽  
Large Family ◽  
Paracellular Permeability ◽  
Paracellular Transport ◽  
Renal Epithelial Cell ◽  
Culture Models ◽  
Epithelial Tight Junction ◽  
Renal Tubular

The epithelial tight junction (TJ) is responsible for the control of paracellular transport between epithelial cells (gate function) and the maintenance of apical/basolateral polarity by preventing the diffusion of membrane lipids and/or proteins from one surface domain to another (fence function). Renal tubule epithelia in the mammalian nephron have TJs that determine paracellular transport characteristics. Paracellular transport across renal tubular epithelial TJs (gate function) varies in different segments of the nephron. A large family of recently identified TJ-associated transmembrane proteins named claudins appear to determine the paracellular permeability properties of the TJ. A combination of inherited human diseases, renal epithelial cell culture models, and nephron expression patterns of claudins is providing important clues about how claudin molecules determine the TJ gate function of renal epithelia in different segments of the nephron.

scholarly journals Tongxinluo Regulates Expression of Tight Junction Proteins and Alleviates Endothelial Cell Monolayer Hyperpermeability via ERK-1/2 Signaling Pathway in Oxidized Low-Density Lipoprotein-Induced Human Umbilical Vein Endothelial Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Chengcheng Chang ◽  
Hongli Liu ◽  
Cong Wei ◽  
Liping Chang ◽  
Junqing Liang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Umbilical Vein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Paracellular Permeability ◽  
Low Density ◽  
Vascular Endothelial ◽  
Oxidized Low Density Lipoprotein ◽  
Umbilical Vein Endothelial Cells

Vascular hyperpermeability resulting from distortion of endothelial junctions is associated with a number of cardiovascular diseases. Endothelial tight junction regulates the paracellular permeability of macromolecules, a function ofHuman Umbilical Vein Endothelial Cells(HUVEC) monolayers that can be regulated byoxidized Low-density Lipoprotein(ox-LDL). However, the understanding of drug regulation of vascular hyperpermeability is so far limited. This study thus aimed to investigate the role ofTongxinluo(TXL) in the maintenance of the vascular endothelial paracellular permeability. Here, changes in permeability were determined by measuring the paracellular flux of FITC-dextran 40000 (FD40), while protein expression and intercellular distribution were examined by western blot and immunofluorescence assay, respectively. We found that TXL alleviated the ox-LDL-induced increase in flux of FD40 and then reduced the hyperpermeability. Moreover, ox-LDL-induced disruptions of ZO-1, occludin, and claudin1 were also restored. This is via the activation of ERK1/2 in the vascular endothelial cells. Our results provide insights into the molecular mechanism by which TXL alleviates ox-LDL-induced hyperpermeability and provide the basis for further investigations of TXL as regulators of vascular barrier function.

The protoplasmic or exoplasmic face association of tight junction particles cannot predict paracellular permeability or heterotypic claudin compatibility

2010 ◽  
Vol 89 (7) ◽  
pp. 547-556 ◽  
Author(s):  
Tetsuichiro Inai ◽  
Tomoki Kamimura ◽  
Eiji Hirose ◽  
Hiroshi Iida ◽  
Yosaburo Shibata
Keyword(s):  
Tight Junction ◽  
Paracellular Permeability

scholarly journals Correlation of occludin protein mobility with paracellular leak pathway permeability in renal epithelia

2018 ◽  
Author(s):  
Josephine Axis ◽  
Alexander L. Kolb ◽  
Robert L. Bacallao ◽  
Kurt Amsler
Keyword(s):  
Tight Junction ◽  
Ischemia Reperfusion Injury ◽  
Mdck Cells ◽  
Ischemia Reperfusion ◽  
Paracellular Permeability ◽  
Tight Junction Protein ◽  
Protein Mobility ◽  
Junction Protein ◽  
Leak Pathway

ABSTRACTStudies have demonstrated regulation of the epithelial paracellular permeability barrier, the tight junction, by a variety of stimuli. Recent studies have reported a correlation between changes in paracellular permeability, particularly paracellular permeability to large solutes (leak pathway), and mobility of the tight junction protein, occludin, in the plane of the plasma membrane. This had led to the hypothesis that changes in occludin protein mobility are causative for changes in paracellular permeability. Using a renal epithelial cell model system, MDCK, we examined the effect of various manipulations on both leak pathway permeability, monitored as the paracellular movement of a fluorescent molecule (calcein), and occludin protein mobility, monitored through fluorescence recovery after photobleaching. Our results indicate that knockdown of the associated tight junction protein, ZO-1, increases baseline leak pathway permeability, whereas, knockdown of the related tight junction protein, ZO-2, does not alter baseline leak pathway permeability. Knockdown of either ZO-1 or ZO-2 decreases the rate of movement of occludin protein but only knockdown of ZO-2 protein alters the percent of occludin protein that is mobile. Further, treatment with hydrogen peroxide increases leak pathway permeability in wild type MDCK cells and in ZO-2 knockdown MDCK cells but not in ZO-1 knockdown MDCK cells. This treatment decreases the rate of occludin movement in all three cell lines but only alters the mobile fraction of occludin protein in ZO-1 knockdown MDCK cells. Finally, we examined the effect of renal ischemia/reperfusion injury on occludin protein mobility in vivo.Ischemia/reperfusion injury both increased the rate of occludin mobility and increased the fraction of occludin protein that is mobile. These results indicate that, at least in our cell culture and in vivo model systems, there is no consistent correlation between paracellular leak pathway permeability and occludin protein mobility.

scholarly journals miR-27a-3p regulates expression of intercellular junctions at the brain endothelium and controls the endothelial barrier permeability

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262152
Author(s):  
Rania Harati ◽  
Saba Hammad ◽  
Abdelaziz Tlili ◽  
Mona Mahfood ◽  
Aloïse Mabondzo ◽  
...  
Keyword(s):  
Tight Junction ◽  
Neurological Disorders ◽  
Adherens Junctions ◽  
Paracellular Permeability ◽  
Endothelial Barrier ◽  
Brain Endothelium ◽  
Barrier Permeability ◽  
Junction Protein ◽  
Endothelial Junctions ◽  
The Brain

Background The brain endothelial barrier permeability is governed by tight and adherens junction protein complexes that restrict paracellular permeability at the blood-brain barrier (BBB). Dysfunction of the inter-endothelial junctions has been implicated in neurological disorders such as multiple sclerosis, stroke and Alzheimer’s disease. The molecular mechanisms underlying junctional dysfunction during BBB impairment remain elusive. MicroRNAs (miRNAs) have emerged as versatile regulators of the BBB function under physiological and pathological conditions, and altered levels of BBB-associated microRNAs were demonstrated in a number of brain pathologies including neurodegeneration and neuroinflammatory diseases. Among the altered micro-RNAs, miR-27a-3p was found to be downregulated in a number of neurological diseases characterized by loss of inter-endothelial junctions and disruption of the barrier integrity. However, the relationship between miR-27a-3p and tight and adherens junctions at the brain endothelium remains unexplored. Whether miR-27a-3p is involved in regulation of the junctions at the brain endothelium remains to be determined. Methods Using a gain-and-loss of function approach, we modulated levels of miR-27a-3p in an in-vitro model of the brain endothelium, key component of the BBB, and examined the resultant effect on the barrier paracellular permeability and on the expression of essential tight and adherens junctions. The mechanisms governing the regulation of junctional proteins by miR-27a-3p were also explored. Results Our results showed that miR-27a-3p inhibitor increases the barrier permeability and causes reduction of claudin-5 and occludin, two proteins highly enriched at the tight junction, while miR-27a-3p mimic reduced the paracellular leakage and increased claudin-5 and occludin protein levels. Interestingly, we found that miR-27-3p induces expression of claudin-5 and occludin by downregulating Glycogen Synthase Kinase 3 beta (GSK3ß) and activating Wnt/ß-catenin signaling, a key pathway required for the BBB maintenance. Conclusion For the first time, we showed that miR-27a-3p is a positive regulator of key tight junction proteins, claudin-5 and occludin, at the brain endothelium through targeting GSK3ß gene and activating Wnt/ß-catenin signaling. Thus, miR-27a-3p may constitute a novel therapeutic target that could be exploited to prevent BBB dysfunction and preserves its integrity in neurological disorders characterized by impairment of the barrier’s function.

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