scholarly journals Tricellular junctions: how to build junctions at the TRICkiest points of epithelial cells

2017 ◽  
Vol 28 (15) ◽  
pp. 2023-2034 ◽  
Author(s):  
Tomohito Higashi ◽  
Ann L. Miller
Keyword(s):  
Epithelial Cells ◽  
Tight Junctions ◽  
Barrier Function ◽  
Hot Spots ◽  
Adherens Junctions ◽  
New Model ◽  
Open Questions ◽  
And Function ◽  
Molecular Components

Tricellular contacts are the places where three cells meet. In vertebrate epithelial cells, specialized structures called tricellular tight junctions (tTJs) and tricellular adherens junctions (tAJs) have been identified. tTJs are important for the maintenance of barrier function, and disruption of tTJ proteins contributes to familial deafness. tAJs have recently been attracting the attention of mechanobiologists because these sites are hot spots of epithelial tension. Although the molecular components, regulation, and function of tTJs and tAJs, as well as of invertebrate tricellular junctions, are beginning to be characterized, many questions remain. Here we broadly cover what is known about tricellular junctions, propose a new model for tension transmission at tAJs, and discuss key open questions.

scholarly journals E–N-cadherin heterodimers define novel adherens junctions connecting endoderm-derived cells

2011 ◽  
Vol 195 (5) ◽  
pp. 873-887 ◽  
Author(s):  
Beate K. Straub ◽  
Steffen Rickelt ◽  
Ralf Zimbelmann ◽  
Christine Grund ◽  
Caecilia Kuhn ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Adherens Junctions ◽  
Tumor Biology ◽  
Intercellular Junctions ◽  
Pivotal Role ◽  
Major Portion ◽  
Tissue Development ◽  
Cadherin Switch ◽  
And Function ◽  
E Cadherin

Intercellular junctions play a pivotal role in tissue development and function and also in tumorigenesis. In epithelial cells, decrease or loss of E-cadherin, the hallmark molecule of adherens junctions (AJs), and increase of N-cadherin are widely thought to promote carcinoma progression and metastasis. In this paper, we show that this “cadherin switch” hypothesis does not hold for diverse endoderm-derived cells and cells of tumors derived from them. We show that the cadherins in a major portion of AJs in these cells can be chemically cross-linked in E–N heterodimers. We also show that cells possessing E–N heterodimer AJs can form semistable hemihomotypic AJs with purely N-cadherin–based AJs of mesenchymally derived cells, including stroma cells. We conclude that these heterodimers are the major AJ constituents of several endoderm-derived tissues and tumors and that the prevailing concept of antagonistic roles of these two cadherins in developmental and tumor biology has to be reconsidered.

PPARγ agonists upregulate the barrier function of tight junctions via a PKC pathway in human nasal epithelial cells

2010 ◽  
Vol 61 (6) ◽  
pp. 489-498 ◽  
Author(s):  
Noriko Ogasawara ◽  
Takashi Kojima ◽  
Mitsuru Go ◽  
Tsuyoshi Ohkuni ◽  
Jun-ichi Koizumi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junctions ◽  
Barrier Function ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells ◽  
Pparγ Agonists

scholarly journals Na,K-ATPase Activity Is Required for Formation of Tight Junctions, Desmosomes, and Induction of Polarity in Epithelial Cells

2001 ◽  
Vol 12 (12) ◽  
pp. 3717-3732 ◽  
Author(s):  
Sigrid A. Rajasekaran ◽  
Lawrence G. Palmer ◽  
Sun Y. Moon ◽  
Alejandro Peralta Soler ◽  
Gerard L. Apodaca ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Atpase Activity ◽  
Tight Junctions ◽  
Stress Fibers ◽  
Epithelial Polarity ◽  
Rhoa Gtpase ◽  
Key Enzyme ◽  
And Function ◽  
Atpase Inhibition ◽  
Darby Canine Kidney

Na,K-ATPase is a key enzyme that regulates a variety of transport functions in epithelial cells. In this study, we demonstrate a role for Na,K-ATPase in the formation of tight junctions, desmosomes, and epithelial polarity with the use of the calcium switch model in Madin-Darby canine kidney cells. Inhibition of Na,K-ATPase either by ouabain or potassium depletion prevented the formation of tight junctions and desmosomes and the cells remained nonpolarized. The formation of bundled stress fibers that appeared transiently in control cells was largely inhibited in ouabain-treated or potassium-depleted cells. Failure to form stress fibers correlated with a large reduction of RhoA GTPase activity in Na,K-ATPase-inhibited cells. In cells overexpressing wild-type RhoA GTPase, Na,K-ATPase inhibition did not affect the formation of stress fibers, tight junctions, or desmosomes, and epithelial polarity developed normally, suggesting that RhoA GTPase is an essential component downstream of Na,K-ATPase-mediated regulation of these junctions. The effects of Na,K-ATPase inhibition were mimicked by treatment with the sodium ionophore gramicidin and were correlated with the increased intracellular sodium levels. Furthermore, ouabain treatment under sodium-free condition did not affect the formation of junctions and epithelial polarity, suggesting that the intracellular Na+ homeostasis plays a crucial role in generation of the polarized phenotype of epithelial cells. These results thus demonstrate that the Na,K-ATPase activity plays an important role in regulating both the structure and function of polarized epithelial cells.

scholarly journals The Interaction of JRAB/MICAL-L2 with Rab8 and Rab13 Coordinates the Assembly of Tight Junctions and Adherens Junctions

2008 ◽  
Vol 19 (3) ◽  
pp. 971-983 ◽  
Author(s):  
Rie Yamamura ◽  
Noriyuki Nishimura ◽  
Hiroyoshi Nakatsuji ◽  
Seiji Arase ◽  
Takuya Sasaki
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Tight Junctions ◽  
Binding Protein ◽  
Adherens Junctions ◽  
Binding Domain ◽  
Endocytic Recycling ◽  
E Cadherin

The assembly of tight junctions (TJs) and adherens junctions (AJs) is regulated by the transport of integral TJ and AJ proteins to and/or from the plasma membrane (PM) and it is tightly coordinated in epithelial cells. We previously reported that Rab13 and a junctional Rab13-binding protein (JRAB)/molecule interacting with CasL-like 2 (MICAL-L2) mediated the endocytic recycling of an integral TJ protein occludin and the formation of functional TJs. Here, we investigated the role of Rab13 and JRAB/MICAL-L2 in the transport of other integral TJ and AJ proteins claudin-1 and E-cadherin to the PM by using a Ca2+-switch model. Although knockdown of Rab13 specifically suppressed claudin-1 and occludin but not E-cadherin transport, knockdown of JRAB/MICAL-L2 and expression of its Rab13-binding domain (JRAB/MICAL-L2-C) inhibited claudin-1, occludin, and E-cadherin transport. We then identified Rab8 as another JRAB/MICAL-L2-C-binding protein. Knockdown of Rab8 inhibited the Rab13-independent transport of E-cadherin to the PM. Rab8 and Rab13 competed with each other for the binding to JRAB/MICAL-L2 and functionally associated with JRAB/MICAL-L2 at the perinuclear recycling/storage compartments and PM, respectively. These results suggest that the interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of AJs and TJs.

scholarly journals Regulation of Tight Junctions in Upper Airway Epithelium

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Takashi Kojima ◽  
Mitsuru Go ◽  
Ken-ichi Takano ◽  
Makoto Kurose ◽  
Tsuyoshi Ohkuni ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Tight Junctions ◽  
Airway Epithelium ◽  
Barrier Function ◽  
Upper Airway ◽  
Mucosal Barrier ◽  
Upper Respiratory Tract ◽  
Junction Molecules ◽  
Human Nasal Epithelial Cells

The mucosal barrier of the upper respiratory tract including the nasal cavity, which is the first site of exposure to inhaled antigens, plays an important role in host defense in terms of innate immunity and is regulated in large part by tight junctions of epithelial cells. Tight junction molecules are expressed in both M cells and dendritic cells as well as epithelial cells of upper airway. Various antigens are sampled, transported, and released to lymphocytes through the cells in nasal mucosa while they maintain the integrity of the barrier. Expression of tight junction molecules and the barrier function in normal human nasal epithelial cells (HNECs) are affected by various stimuli including growth factor, TLR ligand, and cytokine. In addition, epithelial-derived thymic stromal lymphopoietin (TSLP), which is a master switch for allergic inflammatory diseases including allergic rhinitis, enhances the barrier function together with an increase of tight junction molecules in HNECs. Furthermore, respiratory syncytial virus infection in HNECsin vitroinduces expression of tight junction molecules and the barrier function together with proinflammatory cytokine release. This paper summarizes the recent progress in our understanding of the regulation of tight junctions in the upper airway epithelium under normal, allergic, and RSV-infected conditions.

scholarly journals Computational Modeling of Claudin Structure and Function

2020 ◽  
Vol 21 (3) ◽  
pp. 742 ◽  
Author(s):  
Shadi Fuladi ◽  
Ridaka-Wal Jannat ◽  
Le Shen ◽  
Christopher R. Weber ◽  
Fatemeh Khalili-Araghi
Keyword(s):  
Small Molecules ◽  
Tight Junctions ◽  
Barrier Function ◽  
Functional Model ◽  
Structure And Function ◽  
Structural Basis ◽  
Crystallographic Structure ◽  
Epithelial Barrier Function ◽  
Transport Of Ions ◽  
And Function

Tight junctions form a barrier to control passive transport of ions and small molecules across epithelia and endothelia. In addition to forming a barrier, some of claudins control transport properties of tight junctions by forming charge- and size-selective ion channels. It has been suggested claudin monomers can form or incorporate into tight junction strands to form channels. Resolving the crystallographic structure of several claudins in recent years has provided an opportunity to examine structural basis of claudins in tight junctions. Computational and theoretical modeling relying on atomic description of the pore have contributed significantly to our understanding of claudin pores and paracellular transport. In this paper, we review recent computational and mathematical modeling of claudin barrier function. We focus on dynamic modeling of global epithelial barrier function as a function of claudin pores and molecular dynamics studies of claudins leading to a functional model of claudin channels.

scholarly journals Requirement of ZO-1 for the formation of belt-like adherens junctions during epithelial cell polarization

2007 ◽  
Vol 176 (6) ◽  
pp. 779-786 ◽  
Author(s):  
Junichi Ikenouchi ◽  
Kazuaki Umeda ◽  
Sachiko Tsukita ◽  
Mikio Furuse ◽  
Shoichiro Tsukita
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Tight Junctions ◽  
Molecular Mechanisms ◽  
Mutational Analysis ◽  
Adherens Junctions ◽  
Cell Polarization ◽  
Cultured Epithelial Cells

The molecular mechanisms of how primordial adherens junctions (AJs) evolve into spatially separated belt-like AJs and tight junctions (TJs) during epithelial polarization are not well understood. Previously, we reported the establishment of ZO-1/ZO-2–deficient cultured epithelial cells (1[ko]/2[kd] cells), which lacked TJs completely. In the present study, we found that the formation of belt-like AJs was significantly delayed in 1(ko)/2(kd) cells during epithelial polarization. The activation of Rac1 upon primordial AJ formation is severely impaired in 1(ko)/2(kd) cells. Our data indicate that ZO-1 plays crucial roles not only in TJ formation, but also in the conversion from “fibroblastic” AJs to belt-like “polarized epithelial” AJs through Rac1 activation. Furthermore, to examine whether ZO-1 itself mediate belt-like AJ and TJ formation, respectively, we performed a mutational analysis of ZO-1. The requirement for ZO-1 differs between belt-like AJ and TJ formation. We propose that ZO-1 is directly involved in the establishment of two distinct junctional domains, belt-like AJs and TJs, during epithelial polarization.

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