Tight junctions are protein networks. They girdle the endothelial tissues of the intestine, bladder, and brain and perform barrier functions in addition to stabilizing functions. Disturbances of these barrier functions have a negative effect on the different milieus of the body.
What is a tight junction?
Each cell membrane contains different proteins. The individual membrane proteins form a more or less dense network. In this context, a “tight junction,” called a “zonula occludens” in Latin and a “tight junction” in English, is a kind of protein-containing terminal strip that, for example, girdles the epithelial cells of vertebrates and is in close contact with neighboring cell bands. Tight junctions seal the intercellular spaces. They correspond to a barrier of diffusion. Diffusion is a mass transport pathway in the body of living organisms that takes single molecules into the cells. In the form of a diffusion barrier, tight junctions control the flow of molecules into the epithelium. They also prevent the diffusion of membrane components from the apical to the lateral region and vice versa. Through the latter function, they maintain the polarity of the epithelial cells. Tight junctions girdle the renal, urinary bladder, and intestinal epithelium. In addition, they are a functional component of the so-called blood–brain barrier and ensure that substances from the blood cannot diffuse into the tissues of the brain. The terminal ridges of membrane proteins can contain various proteins. Probably not all of them are known yet.
Anatomy and structure
The major membrane proteins within tight junctions are claudins and occludins. Claudins have been documented to be more than 20 different in vertebrates. All integral membrane proteins possess reticular arrangements and connect the membranes of multiple cells informing a head-to-head contact. Aqueous pores make up the anatomy. The composition of the integral membrane proteins differs from epithelium to epithelium and depends on the functional requirements of the tight junctions. THE claudin 16 in the renal epithelium, for example, is involved in the uptake of renal Mg2+ ions into the blood. Tight junctions form different tight networks depending on the task and the epithelium. In the intestine, membrane proteins sit loosely. Those of the blood–brain barrier form a relatively tight barrier. The tightness of the network correlates with permeability. The protein network each consists of narrow strands. Primarily, the extracellular domains of each protein connect to form a cell junction. The intracellular domains attach to the cytoskeleton of cells. In a belt-like manner, tight junctions thus surround the cell circumference of an epithelium and thus nestle against the epithelial cell association.
Function and tasks
Tight junctions are predominantly a diffusion barrier. This function may retain molecules entirely from the intracellular space or be associated with selective permeability (semipermeability) to molecules of certain sizes. The network of tight junctions, through its function as a diffusion barrier, forms the prerequisite for transcytosis. Paracellular diffusion of molecules or ions through the epithelial space is prevented by the tight junctions. At the same time, the tight junctions keep body fluids from escaping. The membrane proteins of the tight junctions also protect the organism from invading microorganisms, thus forming a barrier even for living invaders. In addition to the barrier function, tight junctions have a so-called fence function. The protein network prevents the movement of individual membrane components and thus maintains the cell polarity of the epithelium. The epithelium is divided by the networks into apical and basal regions. The apical cell membrane of the epithelium has a different biochemistry than the basolateral cell membrane. The tight junctions help to maintain these biochemical milieu differences and, by this very fact, enable directional transport of substances. In addition to these functions, there are mechanical functions. For example, tight junctions also serve to stabilize epithelial cell assemblies. They connect the cells of the cytoskeleton with each other and ensure the tissue structure of the epithelium. The permeability between epithelial cells is subject to transient changes. Thus, the epithelium is able to respond to paracellular increased transport demands.To this end, the claudins and occludins of the “dense compounds” associate with the intracellular membrane proteins that establish a connection with the actin cytoskeleton.
Diseases
Tight junctions can undergo altered assembly due to mutations and thus lose their functions. Thus, claudin 16 of the protein networks in the renal epithelium is not present in the required form after mutations of the protein-coding gene. Such mutations may result in Mg2+ loss. Because of the loss of barrier function, too few Mg2+ ions are absorbed from the kidneys into the blood and too many are excreted in the urine. Diseases can also affect the “zonula occludens”. This is especially true for the brain. The blood-brain barrier is a natural diffusion barrier between blood and brain that maintains the milieu of the brain. Disturbances of the blood-brain barrier occur, for example, in the context of multiple sclerosis. However, diseases such as diabetes mellitus can also disrupt the blood-brain barrier. The protective effect of the barrier is also lost in various brain injuries and degenerative diseases. In multiple sclerosis, it is the recurrent inflammation of the brain that has a damaging effect on the tight junctions. The cells of the body’s immune defense system overcome the blood-brain barrier as part of the autoimmune disease. In an ischemic stroke, components of the tight junctions within the blood-brain barrier are actually degraded. This form of stroke is associated with a blood void in the brain, which is subsequently refilled with blood. The endothelia of the blood-brain barrier change in two phases. As oxidants, proteolytic enzymes and cytokines are released by the pathological process, the permeability of the blood-brain barrier changes. Edema develops in the brain. In response, activated leukocytes release so-called matrix metalloproteases, which lead to degradation of the basal lamina and protein complexes in the tight junctions.
