The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Karl Matter - One of the best experts on this subject based on the ideXlab platform.
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Tight Junctions: from simple barriers to multifunctional molecular gates
Nature Reviews Molecular Cell Biology, 2016Co-Authors: Ceniz Zihni, Karl Matter, Clare Mills, Maria S. BaldaAbstract:Tight Junctions are intercellular adhesion complexes in epithelia and endothelia that control paracellular permeability. This paracellular diffusion barrier is semipermeable: it is size- and charge-selective. Paracellular ion permeability at Tight Junctions is largely determined by their claudin composition. Claudins are a family of transmembrane proteins that are thought to form gated ion-selective paracellular pores through the paracellular diffusion barrier. Tight Junctions form the border between the apical and basolateral cell surface domains in polarized epithelia, and support the maintenance of cell polarity by restricting intermixing of apical and basolateral transmembrane components. Tight Junctions are an integral component of the evolutionarily conserved signalling mechanisms that control epithelial-cell polarization and the formation of morphologically and functionally distinct apical domains. Tight Junctions form bidirectional signalling platforms that receive signals from the cell interior, which regulate their assembly and function, and that transduce signals to the cell interior to control cell proliferation, migration, differentiation and survival. Tight Junctions are part of an interconnected network of adhesion complexes that also includes adherens Junctions and focal adhesions. These adhesion complexes crosstalk through direct protein–protein interactions as well as by transmitting signals to each other that influence their assembly and function. Tight Junctions are barriers between epithelial and endothelial cells that regulate the diffusion of molecules across tissues; they also contribute to cell polarity and serve as signalling platforms. Recent findings have broadened our understanding of Tight junction organization, assembly and function. Epithelia and endothelia separate different tissue compartments and protect multicellular organisms from the outside world. This requires the formation of Tight Junctions, selective gates that control paracellular diffusion of ions and solutes. Tight Junctions also form the border between the apical and basolateral plasma-membrane domains and are linked to the machinery that controls apicobasal polarization. Additionally, signalling networks that guide diverse cell behaviours and functions are connected to Tight Junctions, transmitting information to and from the cytoskeleton, nucleus and different cell adhesion complexes. Recent advances have broadened our understanding of the molecular architecture and cellular functions of Tight Junctions.
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Tight Junctions from simple barriers to multifunctional molecular gates
Nature Reviews Molecular Cell Biology, 2016Co-Authors: Ceniz Zihni, Karl Matter, Clare Mills, Maria S. BaldaAbstract:Epithelia and endothelia separate different tissue compartments and protect multicellular organisms from the outside world. This requires the formation of Tight Junctions, selective gates that control paracellular diffusion of ions and solutes. Tight Junctions also form the border between the apical and basolateral plasma-membrane domains and are linked to the machinery that controls apicobasal polarization. Additionally, signalling networks that guide diverse cell behaviours and functions are connected to Tight Junctions, transmitting information to and from the cytoskeleton, nucleus and different cell adhesion complexes. Recent advances have broadened our understanding of the molecular architecture and cellular functions of Tight Junctions.
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Tight Junctions as regulators of tissue remodelling.
Current Opinion in Cell Biology, 2016Co-Authors: Maria S. Balda, Karl MatterAbstract:Formation of tissue barriers by epithelial and endothelial cells requires neighbouring cells to interact via intercellular Junctions, which includes Tight Junctions. Tight Junctions form a semipermeable paracellular diffusion barrier and act as signalling hubs that guide cell behaviour and differentiation. Components of Tight Junctions are also expressed in cell types not forming Tight Junctions, such as cardiomyocytes, where they associate with facia adherens and/or gap Junctions. This review will focus on Tight junction proteins and their importance in tissue homeostasis and remodelling with a particular emphasis on what we have learned from animal models and human diseases.
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Signalling at Tight Junctions during epithelial differentiation and microbial pathogenesis
Journal of Cell Science, 2014Co-Authors: Ceniz Zihni, Maria S. Balda, Karl MatterAbstract:Tight Junctions are a component of the epithelial junctional complex, and they form the paracellular diffusion barrier that enables epithelial cells to create cellular sheets that separate compartments with different compositions. The assembly and function of Tight Junctions are intimately linked to the actomyosin cytoskeleton and, hence, are under the control of signalling mechanisms that regulate cytoskeletal dynamics. Tight Junctions not only receive signals that guide their assembly and function, but transmit information to the cell interior to regulate cell proliferation, migration and survival. As a crucial component of the epithelial barrier, they are often targeted by pathogenic viruses and bacteria, aiding infection and the development of disease. In this Commentary, we review recent progress in the understanding of the molecular signalling mechanisms that drive junction assembly and function, and the signalling processes by which Tight Junctions regulate cell behaviour and survival. We also discuss the way in which junctional components are exploited by pathogenic viruses and bacteria, and how this might affect junctional signalling mechanisms.
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SnapShot: Epithelial Tight Junctions
Cell, 2014Co-Authors: Karl Matter, Maria S. BaldaAbstract:Tight Junctions form a morphological and functional border between the apical and basolateral cell surface domains that serves as a paracellular diffusion barrier, enabling epithelial cells to separate compartments of different composition. Tight Junctions also contribute to the generation and maintenance of cell polarity and regulate signaling mechanisms that guide cell behavior, shape, and gene expression. This SnapShot illustrates their components, organization, and functions.
Maria S. Balda - One of the best experts on this subject based on the ideXlab platform.
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Tight Junctions: from simple barriers to multifunctional molecular gates
Nature Reviews Molecular Cell Biology, 2016Co-Authors: Ceniz Zihni, Karl Matter, Clare Mills, Maria S. BaldaAbstract:Tight Junctions are intercellular adhesion complexes in epithelia and endothelia that control paracellular permeability. This paracellular diffusion barrier is semipermeable: it is size- and charge-selective. Paracellular ion permeability at Tight Junctions is largely determined by their claudin composition. Claudins are a family of transmembrane proteins that are thought to form gated ion-selective paracellular pores through the paracellular diffusion barrier. Tight Junctions form the border between the apical and basolateral cell surface domains in polarized epithelia, and support the maintenance of cell polarity by restricting intermixing of apical and basolateral transmembrane components. Tight Junctions are an integral component of the evolutionarily conserved signalling mechanisms that control epithelial-cell polarization and the formation of morphologically and functionally distinct apical domains. Tight Junctions form bidirectional signalling platforms that receive signals from the cell interior, which regulate their assembly and function, and that transduce signals to the cell interior to control cell proliferation, migration, differentiation and survival. Tight Junctions are part of an interconnected network of adhesion complexes that also includes adherens Junctions and focal adhesions. These adhesion complexes crosstalk through direct protein–protein interactions as well as by transmitting signals to each other that influence their assembly and function. Tight Junctions are barriers between epithelial and endothelial cells that regulate the diffusion of molecules across tissues; they also contribute to cell polarity and serve as signalling platforms. Recent findings have broadened our understanding of Tight junction organization, assembly and function. Epithelia and endothelia separate different tissue compartments and protect multicellular organisms from the outside world. This requires the formation of Tight Junctions, selective gates that control paracellular diffusion of ions and solutes. Tight Junctions also form the border between the apical and basolateral plasma-membrane domains and are linked to the machinery that controls apicobasal polarization. Additionally, signalling networks that guide diverse cell behaviours and functions are connected to Tight Junctions, transmitting information to and from the cytoskeleton, nucleus and different cell adhesion complexes. Recent advances have broadened our understanding of the molecular architecture and cellular functions of Tight Junctions.
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Tight Junctions from simple barriers to multifunctional molecular gates
Nature Reviews Molecular Cell Biology, 2016Co-Authors: Ceniz Zihni, Karl Matter, Clare Mills, Maria S. BaldaAbstract:Epithelia and endothelia separate different tissue compartments and protect multicellular organisms from the outside world. This requires the formation of Tight Junctions, selective gates that control paracellular diffusion of ions and solutes. Tight Junctions also form the border between the apical and basolateral plasma-membrane domains and are linked to the machinery that controls apicobasal polarization. Additionally, signalling networks that guide diverse cell behaviours and functions are connected to Tight Junctions, transmitting information to and from the cytoskeleton, nucleus and different cell adhesion complexes. Recent advances have broadened our understanding of the molecular architecture and cellular functions of Tight Junctions.
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Tight Junctions as regulators of tissue remodelling.
Current Opinion in Cell Biology, 2016Co-Authors: Maria S. Balda, Karl MatterAbstract:Formation of tissue barriers by epithelial and endothelial cells requires neighbouring cells to interact via intercellular Junctions, which includes Tight Junctions. Tight Junctions form a semipermeable paracellular diffusion barrier and act as signalling hubs that guide cell behaviour and differentiation. Components of Tight Junctions are also expressed in cell types not forming Tight Junctions, such as cardiomyocytes, where they associate with facia adherens and/or gap Junctions. This review will focus on Tight junction proteins and their importance in tissue homeostasis and remodelling with a particular emphasis on what we have learned from animal models and human diseases.
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Signalling at Tight Junctions during epithelial differentiation and microbial pathogenesis
Journal of Cell Science, 2014Co-Authors: Ceniz Zihni, Maria S. Balda, Karl MatterAbstract:Tight Junctions are a component of the epithelial junctional complex, and they form the paracellular diffusion barrier that enables epithelial cells to create cellular sheets that separate compartments with different compositions. The assembly and function of Tight Junctions are intimately linked to the actomyosin cytoskeleton and, hence, are under the control of signalling mechanisms that regulate cytoskeletal dynamics. Tight Junctions not only receive signals that guide their assembly and function, but transmit information to the cell interior to regulate cell proliferation, migration and survival. As a crucial component of the epithelial barrier, they are often targeted by pathogenic viruses and bacteria, aiding infection and the development of disease. In this Commentary, we review recent progress in the understanding of the molecular signalling mechanisms that drive junction assembly and function, and the signalling processes by which Tight Junctions regulate cell behaviour and survival. We also discuss the way in which junctional components are exploited by pathogenic viruses and bacteria, and how this might affect junctional signalling mechanisms.
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SnapShot: Epithelial Tight Junctions
Cell, 2014Co-Authors: Karl Matter, Maria S. BaldaAbstract:Tight Junctions form a morphological and functional border between the apical and basolateral cell surface domains that serves as a paracellular diffusion barrier, enabling epithelial cells to separate compartments of different composition. Tight Junctions also contribute to the generation and maintenance of cell polarity and regulate signaling mechanisms that guide cell behavior, shape, and gene expression. This SnapShot illustrates their components, organization, and functions.
Hideki Chiba - One of the best experts on this subject based on the ideXlab platform.
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doi:10.1155/2011/253048 Review Article Possible Involvement of Tight Junctions, Extracellular Matrix and Nuclear Receptors in Epithelial Differentiation
2013Co-Authors: Naoki Ichikawa-tomikawa, Seiro Satohisa, Kotaro Sugimoto, Keisuke Nishiura, Hideki ChibaAbstract:Copyright © 2011 Naoki Ichikawa-Tomikawa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Tight Junctions are intercellular Junctions localized at the most apical end of the lateral plasma membrane. They consist of four kinds of transmembrane proteins (occludin, claudins, junctional adhesion molecules, and tricellulin) and huge numbers of scaffolding proteins and contribute to the paracellular barrier and fence function. The mutation and deletion of these proteins impair the functions of Tight Junctions and cause various human diseases. In this paper, we provide an overview of recent studies on transmembrane proteins of Tight Junctions and highlight the functional significance of Tight Junctions, extracellular matrix, and nuclear receptors in epithelial differentiation. 1
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Possible Involvement of Tight Junctions, Extracellular Matrix and Nuclear Receptors in Epithelial Differentiation
Journal of biomedicine & biotechnology, 2011Co-Authors: Naoki Ichikawa-tomikawa, Seiro Satohisa, Kotaro Sugimoto, Keisuke Nishiura, Hideki ChibaAbstract:Tight Junctions are intercellular Junctions localized at the most apical end of the lateral plasma membrane. They consist of four kinds of transmembrane proteins (occludin, claudins, junctional adhesion molecules, and tricellulin) and huge numbers of scaffolding proteins and contribute to the paracellular barrier and fence function. The mutation and deletion of these proteins impair the functions of Tight Junctions and cause various human diseases. In this paper, we provide an overview of recent studies on transmembrane proteins of Tight Junctions and highlight the functional significance of Tight Junctions, extracellular matrix, and nuclear receptors in epithelial differentiation.
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Transmembrane proteins of Tight Junctions.
Biochimica et biophysica acta, 2007Co-Authors: Hideki Chiba, Takashi Kojima, Masaki Murata, Makoto Osanai, Norimasa SawadaAbstract:Tight Junctions contribute to the paracellular barrier, the fence dividing plasma membranes, and signal transduction, acting as a multifunctional complex in vertebrate epithelial and endothelial cells. The identification and characterization of the transmembrane proteins of Tight Junctions, claudins, junctional adhesion molecules (JAMs), occludin and tricellulin, have led to insights into the molecular nature of Tight Junctions. We provide an overview of recent progress in studies on these proteins and highlight their roles and regulation, as well as their functional significance in human diseases.
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Tight Junctions and human diseases.
Medical electron microscopy : official journal of the Clinical Electron Microscopy Society of Japan, 2003Co-Authors: Norimasa Sawada, Takashi Kojima, Masaki Murata, Makoto Osanai, Keisuke Kikuchi, Hirotoshi Tobioka, Hideki ChibaAbstract:Tight Junctions are intercellular Junctions adjacent to the apical end of the lateral membrane surface. They have two functions, the barrier (or gate) function and the fence function. The barrier function of Tight Junctions regulates the passage of ions, water, and various macromolecules, even of cancer cells, through paracellular spaces. The barrier function is thus relevant to edema, jaundice, diarrhea, and blood-borne metastasis. On the other hand, the fence function maintains cell polarity. In other words, Tight Junctions work as a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell biology, in terms of loss of cell polarity. Of the proteins comprising Tight Junctions, integral membrane proteins occludin, claudins, and JAMs have been recently discovered. Of these molecules, claudins are exclusively responsible for the formation of Tight-junction strands and are connected with the actin cytoskeleton mediated by ZO-1. Thus, both functions of Tight Junctions are dependent on the integrity of the actin cytoskeleton as well as ATP. Mutations in the claudin14 and the claudin16 genes result in hereditary deafness and hereditary hypomagnesemia, respectively. Some pathogenic bacteria and viruses target and affect the Tight-junction function, leading to diseases. In this review, the relationship between Tight Junctions and human diseases is summarized.
Mikio Furuse - One of the best experts on this subject based on the ideXlab platform.
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Molecular organization of tricellular Tight Junctions
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 2014Co-Authors: Mikio FuruseAbstract:Within an epithelial cellular sheet, the paracellular pathway can be divided into two routes: one between two adjacent cells and one at tricellular contacts, where the vertices of three cells meet. For epithelial barrier function, Tight Junctions restrict solute permeability through the paracellular pathway between two cells, while tricellular contacts contain specialized structures of Tight Junctions, named tricellular Tight Junctions (tTJs). Two types of membrane proteins, tricellulin and angulin family proteins (angulin-1/LSR, angulin-2/ILDR1 and angulin-3/ILDR2) have been identified as molecular components of tTJs. Angulins recruit triellulin to tTJs and these tTJ-associated proteins are required for normal tTJ formation as well as strong epithelial barrier function. Furthermore, mutations in tricellulin and angulin-2/ILDR1 genes cause autosomal recessive familial deafness, DFNB49 and DFNB42, respectively. Further analyses of the angulin-tricellulin system should lead to better understanding of the molecular mechanism and regulation of tTJs.
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Molecular organization of tricellular Tight Junctions
Tissue barriers, 2014Co-Authors: Mikio Furuse, Yukako Oda, Tomohito Higashi, Yasushi Izumi, Noriko IwamotoAbstract:When the apicolateral border of epithelial cells is compared with a polygon, its sides correspond to the apical junctional complex, where cell adhesion molecules assemble from the plasma membranes of two adjacent cells. On the other hand, its vertices correspond to tricellular contacts, where the corners of three cells meet. Vertebrate tricellular contacts have specialized structures of Tight Junctions, termed tricellular Tight Junctions (tTJs). tTJs were identified by electron microscopic observations more than 40 years ago, but have been largely forgotten in epithelial cell biology since then. The identification of tricellulin and angulin family proteins as tTJ-associated membrane proteins has enabled us to study tTJs in terms of not only the paracellular barrier function but also unknown characteristics of epithelial cell corners via molecular biological approaches.
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Molecular architecture of Tight Junctions of periderm differs from that of the maculae occludentes of epidermis.
The Journal of investigative dermatology, 2002Co-Authors: Kazumasa Morita, Mikio Furuse, Yoko Yoshida, Masahiko Itoh, Hiroyuki Sasaki, Shoichiro Tsukita, Yoshiki MiyachiAbstract:Occludin and claudins are tetraspan-transmembrane proteins in Tight Junctions. Maculae occludentes, which are less-developed Tight Junctions, occur in the granular cell layer of the epidermis. The periderm, which overlies the developing epidermis and functions as a protective layer for the embryo, carries developed Tight Junctions as observed in simple epithelia. In both periderm and epidermis, occludin is expressed at the cell–cell border. To determine the difference between Tight Junctions of periderm and epidermis, claudin-6 expression was examined in periderm and epidermis. Immunofluorescence staining showed claudin-6 expression at the cell–cell border of the periderm, but not in the epidermis. Reverse transcription–polymerase chain reaction confirmed that claudin-6 was not expressed in mouse adult skin, whereas immunoelectron microscopy revealed that claudin-6 was localized at Tight Junctions of the periderm. Furthermore, L fibroblasts with stable expression of exogenous claudin-6 formed developed Tight Junctions at cell–cell borders. These findings indicate that molecular architecture of Tight Junctions of the periderm is different from that of the maculae occludentes of the epidermis, and that claudin-6 is important in the formation of Tight Junctions of the periderm.
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Multifunctional strands in Tight Junctions.
Nature Reviews Molecular Cell Biology, 2001Co-Authors: Shoichiro Tsukita, Mikio Furuse, Masahiko ItohAbstract:Tight Junctions are one mode of cell–cell adhesion in epithelial and endothelial cellular sheets. They act as a primary barrier to the diffusion of solutes through the intercellular space, create a boundary between the apical and the basolateral plasma membrane domains, and recruit various cytoskeletal as well as signalling molecules at their cytoplasmic surface. New insights into the molecular architecture of Tight Junctions allow us to now discuss the structure and functions of this unique cell–cell adhesion apparatus in molecular terms.
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occludin a novel integral membrane protein localizing at Tight Junctions
Journal of Cell Biology, 1993Co-Authors: Mikio Furuse, Tetsuaki Hirase, M Itoh, Akira Nagafuchi, Shigenobu Yonemura, Shoichiro TsukitaAbstract:Recently, we found that ZO-1, a Tight junction-associated protein, was concentrated in the so called isolated adherens junction fraction from the liver (Itoh, M., A. Nagafuchi, S. Yonemura, T. Kitani-Yasuda, Sa. Tsukita, and Sh. Tsukita. 1993. J. Cell Biol. 121:491-502). Using this fraction derived from chick liver as an antigen, we obtained three monoclonal antibodies specific for a approximately 65-kD protein in rats. This antigen was not extractable from plasma membranes without detergent, suggesting that it is an integral membrane protein. Immunofluorescence and immunoelectron microscopy with these mAbs showed that this approximately 65-kD membrane protein was exclusively localized at Tight Junctions of both epithelial and endothelial cells: at the electron microscopic level, the labels were detected directly over the points of membrane contact in Tight Junctions. To further clarify the nature and structure of this membrane protein, we cloned and sequenced its cDNA. We found that the cDNA encoded a 504-amino acid polypeptide with 55.9 kDa. A search of the data base identified no proteins with significant homology to this membrane protein. A most striking feature of its primary structure was revealed by a hydrophilicity plot: four putative membrane-spanning segments were included in the NH2-terminal half. This hydrophilicity plot was very similar to that of connexin, an integral membrane protein in gap Junctions. These findings revealed that an integral membrane protein localizing at Tight Junctions is now identified, which we designated as "occludin."
Ayyappan K. Rajasekaran - One of the best experts on this subject based on the ideXlab platform.
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Na,K-ATPase and epithelial Tight Junctions.
Frontiers in Bioscience, 2009Co-Authors: Sigrid A. Rajasekaran, Ayyappan K. RajasekaranAbstract:: Tight Junctions are unique organelles in polarized epithelial and endothelial cells that regulate the flow of solutes and ions across the epithelial barrier. The structure and functions of Tight Junctions are regulated by a wide variety of signaling and molecular mechanisms. Several recent studies in mammals, drosophila, and zebrafish reported a new role for Na,K-ATPase, a well-studied ion transporter, in the modulation of Tight junction development, permeability, and polarity. In this review, we have attempted to compile these new reports and suggest a model for a conserved role of Na,K-ATPase in the regulation of Tight junction structure and functions.
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Interactions of Tight Junctions with membrane channels and transporters.
Biochimica et Biophysica Acta, 2007Co-Authors: Sigrid A. Rajasekaran, Klaus W. Beyenbach, Ayyappan K. RajasekaranAbstract:Tight Junctions are unique organelles in epithelial cells. They are localized to the apico-lateral region and essential for the epithelial cell transport functions. The paracellular transport process that occurs via Tight Junctions is extensively studied and is intricately regulated by various extracellular and intracellular signals. Fine regulation of this transport pathway is crucial for normal epithelial cell functions. Among factors that control Tight junction permeability are ions and their transporters. However, this area of research is still in its infancy and much more needs to be learned about how these molecules regulate Tight junction structure and functions. In this review we have attempted to compile literature on ion transporters and channels involved in the regulation of Tight Junctions.
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Role of Na-K-ATPase in the assembly of Tight Junctions
American Journal of Physiology-renal Physiology, 2003Co-Authors: Ayyappan K. Rajasekaran, Sigrid A. RajasekaranAbstract:Na-K-ATPase, also known as the sodium pump, is a crucial enzyme that regulates intracellular sodium homeostasis in mammalian cells. In epithelial cells Na-K-ATPase function is also involved in the formation of Tight Junctions through RhoA GTPase and stress fibers. In this review, a new two-step model for the assembly of Tight Junctions is proposed: step 1, an E-cadherin-dependent formation of partial Tight junction strands and of the circumferential actin ring; and step 2, active actin polymerization-dependent tethering of Tight junction strands to form functional Tight Junctions, an event requiring normal function of Na-K-ATPase in epithelial cells. A new role for stress fibers in the assembly of Tight Junctions is proposed. Also, implications of Na-K-ATPase function on Tight junction assembly in diseases such as cancer, ischemia, hypomagnesemia, and polycystic kidney disease are discussed.