Tight junctions, also known as occluding junctions or zonulae occludentes (singular, zonula occludens), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epithelial cells.They also play a critical role maintaining the structure and permeability of endothelial cells. Tight junctions may also serve as leaky pathways by forming selective channels for small cations, anions, or water. The corresponding junctions that occur in invertebrates are septate junctions.
Tight junctions are composed of a branching network of sealing strands, each strand acting independently from the others. Therefore, the efficiency of the junction in preventing ion passage increases exponentially with the number of strands. Each strand is formed from a row of transmembrane proteins embedded in both plasma membranes, with extracellular domains joining one another directly. There are at least 40 different proteins composing the tight junctions.These proteins consist of both transmembrane and cytoplasmic proteins. The three major transmembrane proteins are occludin, claudins, and junction adhesion molecule (JAM) proteins. These associate with different peripheral membrane proteins such as ZO-1 located on the intracellular side of plasma membrane, which anchor the strands to the actin component of the cytoskeleton. Thus, tight junctions join together the cytoskeletons of adjacent cells.
They perform vital functions:
Epithelia are classed as "tight" or "leaky", depending on the ability of the tight junctions to prevent water and solute movement:
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellular matrix. Epithelial tissues line the outer surfaces of organs and blood vessels throughout the body, as well as the inner surfaces of cavities in many internal organs. An example is the epidermis, the outermost layer of the skin.
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indirect interaction, where cells attach to surrounding extracellular matrix, a gel-like structure containing molecules released by cells into spaces between them. Cells adhesion occurs from the interactions between cell-adhesion molecules (CAMs), transmembrane proteins located on the cell surface. Cell adhesion links cells in different ways and can be involved in signal transduction for cells to detect and respond to changes in the surroundings. Other cellular processes regulated by cell adhesion include cell migration and tissue development in multicellular organisms. Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. Cell adhesion is also essential for infectious organisms, such as bacteria or viruses, to cause diseases.
Cell junctions or junctional complexes, are a class of cellular structures consisting of multiprotein complexes that provide contact or adhesion between neighboring cells or between a cell and the extracellular matrix in animals. They also maintain the paracellular barrier of epithelia and control paracellular transport. Cell junctions are especially abundant in epithelial tissues. Combined with cell adhesion molecules and extracellular matrix, cell junctions help hold animal cells together.
Claudins are a family of proteins which, along with occludin, are the most important components of the tight junctions. Tight junctions establish the paracellular barrier that controls the flow of molecules in the intercellular space between the cells of an epithelium. They have four transmembrane domains, with the N-terminus and the C-terminus in the cytoplasm.
Transcytosis is a type of transcellular transport in which various macromolecules are transported across the interior of a cell. Macromolecules are captured in vesicles on one side of the cell, drawn across the cell, and ejected on the other side. Examples of macromolecules transported include IgA, transferrin, and insulin. While transcytosis is most commonly observed in epithelial cells, the process is also present elsewhere. Blood capillaries are a well-known site for transcytosis, though it occurs in other cells, including neurons, osteoclasts and M cells of the intestine.
Occludin is an enzyme that oxidizes NADH. It was first identified in epithelial cells as a 65 kDa integral plasma-membrane protein localized at the tight junctions. Together with Claudins, and zonula occludens-1 (ZO-1), occludin has been considered a staple of tight junctions, and although it was shown to regulate the formation, maintenance, and function of tight junctions, its precise mechanism of action remained elusive and most of its actions were initially attributed to conformational changes following selective phosphorylation, and its redox-sensitive dimerization. However, mounting evidence demonstrated that occludin is not only present in epithelial/endothelial cells, but is also expressed in large quantities in cells that do not have tight junctions but have very active metabolism: pericytes, neurons and astrocytes, oligodendrocytes, dendritic cells, monocytes/macrophages lymphocytes, and myocardium. Recent work, using molecular modeling, supported by biochemical and live-cell experiments in human cells demonstrated that occludin is a NADH oxidase that influences critical aspects of cell metabolism like glucose uptake, ATP production and gene expression. Furthermore, manipulation of occludin content in human cells is capable of influencing the expression of glucose transporters, and the activation of transcription factors like NFkB, and histone deacetylases like sirtuins, which proved capable of diminishing HIV replication rates in infected human macrophages under laboratory conditions.
Paracellular transport refers to the transfer of substances across an epithelium by passing through the intercellular space between the cells. It is in contrast to transcellular transport, where the substances travel through the cell, passing through both the apical membrane and basolateral membrane.
Zonula occludens-1 ZO-1, also known as Tight junction protein-1 is a 220-kD peripheral membrane protein that is encoded by the TJP1 gene in humans. It belongs to the family of zonula occludens proteins, which are tight junction-associated proteins and of which, ZO-1 is the first to be cloned. It was first isolated in 1986 by Stevenson and Goodenough using a monoclonal antibody raised in rodent liver to recognise a 225-kD polypeptide in whole liver homogenates and in tight junction-enriched membrane fractions. It has a role as a scaffold protein which cross-links and anchors Tight Junction (TJ) strand proteins, which are fibril-like structures within the lipid bilayer, to the actin cytoskeleton.
Claudin-1 is a protein that in humans is encoded by the CLDN1 gene. It belongs to the group of claudins.
Claudin-5 is a protein that in humans is encoded by the CLDN5 gene. It belongs to the group of claudins.
Claudin 3, also known as CLDN3, is a protein which in humans is encoded by the CLDN3 gene. It is a member of the claudin protein family.
Claudin-2 is a protein that in humans is encoded by the CLDN2 gene. It belongs to the group of claudins.
Claudin-14 is a protein that in humans is encoded by the CLDN14 gene. It belongs to a related family of proteins called claudins.
Claudin-15 is a protein that in humans is encoded by the CLDN15 gene. It belongs to the group of claudins. Among its related pathways are Blood-Brain Barrier and Immune Cell Transmigration: VCAM-1/CD106 Signaling Pathways and Tight junction. GO annotations related to this gene include identical protein binding and structural molecule activity. An important paralog of this gene is CLDN10.
The intestinal epithelium is the single cell layer that form the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelial cells, it serves two main functions: absorbing useful substances into the body and restricting the entry of harmful substances. As part of its protective role, the intestinal epithelium forms an important component of the intestinal mucosal barrier. Certain diseases and conditions are caused by functional defects in the intestinal epithelium. On the other hand, various diseases and conditions can lead to its dysfunction which, in turn, can lead to further complications.
Epithelial polarity is one example of the cell polarity that is a fundamental feature of many types of cells. Epithelial cells feature distinct 'apical', 'lateral' and 'basal' plasma membrane domains. Epithelial cells connect to one another via their lateral membranes to form epithelial sheets that line cavities and surfaces throughout the animal body. Each plasma membrane domain has a distinct protein composition, giving them distinct properties and allowing directional transport of molecules across the epithelial sheet. How epithelial cells generate and maintain polarity remains unclear, but certain molecules have been found to play a key role.
Cell–cell interaction refers to the direct interactions between cell surfaces that play a crucial role in the development and function of multicellular organisms. These interactions allow cells to communicate with each other in response to changes in their microenvironment. This ability to send and receive signals is essential for the survival of the cell. Interactions between cells can be stable such as those made through cell junctions. These junctions are involved in the communication and organization of cells within a particular tissue. Others are transient or temporary such as those between cells of the immune system or the interactions involved in tissue inflammation. These types of intercellular interactions are distinguished from other types such as those between cells and the extracellular matrix. The loss of communication between cells can result in uncontrollable cell growth and cancer.
Septate junctions are intercellular junctions found in invertebrate epithelial cells, appearing as ladder-like structures under electron microscopy. They are thought to provide structural strength and a barrier to solute diffusion through the intercellular space. They are considered somewhat analogous to the (vertebrate) tight junctions; however, tight and septate junctions are different in many ways. Known insect homologues of tight junction components are components of conserved signalling pathways that localize to either adherens junctions, the subapical complex, or the marginal zone. Recent studies show that septate junctions are also identified in the myelinated nerve fibers of the vertebrates.
The internal surface of the uterus is lined by uterine epithelial cells which undergo dramatic changes during pregnancy. The role of the uterine epithelial cells is to selectively allow the blastocyst to implant at a specific time. All other times of the cycle, these uterine epithelial cells are refractory to blastocyst implantation. Uterine epithelial cells have a similar structure in most species and the changes which occur in the uterine epithelial cells at the time of blastocyst implantation are also conserved among most species.
Tight junction proteins are molecules situated at the tight junctions of epithelial, endothelial and myelinated cells. This multiprotein junctional complex has a regulatory function in passage of ions, water and solutes through the paracellular pathway. It can also coordinate the motion of lipids and proteins between the apical and basolateral surfaces of the plasma membrane. Thereby tight junction conducts signaling molecules, that influence the differentiation, proliferation and polarity of cells. So tight junction plays a key role in maintenance of osmotic balance and trans-cellular transport of tissue specific molecules. Nowadays is known more than 40 different proteins, that are involved in these selective TJ channels.