Pathogens Target Tight Junction Proteins
Proteolytic enzymes from pollen, many viruses, dust mites, and enterotoxins from bacteria, like
Clostridium perfringens, interact with these junctions to bring about the loss of the epithelial barrier function.
A cell junction is a multiprotein complex that links two neighboring cells or a cell to the extracellular matrix. These complexes form the barriers guarding the intercellular spaces, and thus, control the paracellular transport. They help in establishing communication between neighboring cells.
There are three basic types of cell junctions: anchoring junction, communicating or GAP junctions, and tight junctions. Anchoring junctions are protein complexes that are used to anchor the cells of a tissue either to each other or to the extracellular matrix. Communicating junctions bring about direct chemical communication between adjacent cells. Tight junctions act as barriers that regulate the movement of ions, water, and other molecule via the paracellular space in the epithelial cells. We will now elaborate on the tight junctions in this article.
What are Tight Junctions?
These are also known as occluding junctions or zonulae occludentes. These junctions form the closest contacts as compared to the other cell junctions and can therefore form a barrier that is virtually impermeable to fluids. These are the most apical structures of the apical complex, and they form the demarcation between the apical and the basolateral membranes of the domains.
Where are Tight Junctions Found in the Body?
Tight junctions are required for cell adhesion in various tissues of the body. These structures are seen to be present on the epithelium cells that form the internal lining of the body. These are usually of one or two layers of cells. Recent studies have also highlighted their role in barrier function in the skin as well.
Numerous and highly complex tight junctions are usually found in the epithelial lining of the distal convoluted tubules, the collecting duct of nephrons, the blood brain barrier, and the part of the bile duct that transverses the liver. These linings are thus given the name "tight epithelia".
Relatively fewer number and less complex tight junctions are present on the epithelial lining of the proximal tubules of the kidney. These linings are called "leaky epithelia".
What is the Structure of Tight Junctions?
Tight junctions are usually made of transmembrane proteins that are linked to a cytoplasmic plaque. Transmembrane proteins are usually of two types: tetraspan and single-span transmembrane proteins. Tetraspan proteins contain four membrane spanning domains, these include proteins like occludins, claudins, and tricellulins.
Occludins regulate the diffusion of hydrophilic molecules; they are usually associated with the intramembrane strand of the actin filament. Claudins determine the ion selectivity of tight junctions and are required for junction assembly. Tricellulins are found in junctions with three cells and are required to bring about cell-cell adhesion.
Single-span transmembrane proteins include Junctional Adhesion Molecules (JAMs). JAM protein is required for adhesion between the endothelial cells and leukocytes as well as for maintaining cell polarization.
The cytoplasmic plaque is formed by a network of scaffolding and adaptor proteins, that are bound to cell signaling components as well as to the components of the cytoskeleton such as actin filaments. This complex acts as an interface between junctional membrane proteins and the cytoskeletal protein. ZO-1 is a scaffolding protein that interacts with membrane proteins like claudins and cell signaling protein. ZO-2 and ZO-3 are adaptor proteins that bind to membrane proteins like occludin.
Tight junctions occur in a belt completely encircling the cells, for a solute, ion, or molecule to pass through the layer of cells, it has to be first taken inside the cell from one end and given out from the other side. The junctional membrane proteins are arranged like beads on a thread of the cytoskeletal filaments and are cross-linked to each other.
What are the Functions of Tight Junctions?
They two main functions of Tight Junctions include paracellular permeability and regulation of cell proliferation and polarization. As these multiprotein complexes are negatively charged, they selectively allow positively charged ions to pass through. These junctions are also known to be size selective―molecules with radii greater than 4.5 °A are usually excluded. These junctions may also determine the permeability of certain hydrophilic molecules via the paracellular space. Physiological pH also seems to determine the permeability of these molecules.
Cell proliferation and regulation seems to play a major role in the development of differentiated tissues. Occludins present in tight junctions are required for suppression of cell proliferation, and the absence of these proteins may lead to uncontrolled cancerous growth of cells. Certain biochemical studies indicate that tight junctions are required for the maintenance of apico-basal polarity. Proteins that are required for cell polarization usually form the complexes at tight junctions.
Occludins are also seen to regulate migration of neutrophils across the epithelial cell layer. Claudins also function to regulate cell migration.