Tight junctions (TJs), also known as zonulae occludentes, are specialized multiprotein complexes composed of claudins and occludins that fuse the outer layers of adjacent cell membranes together. Their primary function is to create a virtually impermeable barrier, regulating the movement of water and solutes through the space between cells. This dynamically controlled barrier allows tissues to maintain distinct chemical environments on either side of a cellular sheet.
Tight Junctions in Epithelial Linings
Tight junctions are most common in epithelial tissues, which line the body’s surfaces and internal cavities. In these linings, TJs separate the internal environment from the external world or organ contents. This separation blocks paracellular transport, forcing substances to pass through the cells rather than between them.
The gastrointestinal tract, from the stomach to the colon, is a prime example where TJs form a selective barrier. They prevent the leakage of digestive enzymes, bacteria, and toxins from the gut lumen into underlying tissues. Although generally tight, the barrier is selectively permeable; for instance, claudin-2 can form regulated channels allowing controlled passage of certain ions and water necessary for nutrient absorption.
TJs in the respiratory tract’s epithelial lining protect lung tissue from airborne pathogens and irritants. The epidermis also relies on TJs to minimize water loss and shield against foreign substances. The efficiency of this seal varies by location; “tighter” epithelia, such as the bladder, exhibit higher electrical resistance than “leaky” epithelia, like the proximal kidney tubule.
Creating Highly Selective Endothelial Barriers
Tight junctions form selective barriers within the vascular system, protecting sensitive organs. The Blood-Brain Barrier (BBB) consists of specialized endothelial cells lining the brain’s capillaries, and its restrictive nature is due to robust tight junctions. These junctions are less permeable than those in general circulation, limiting the passage of large and most water-soluble small molecules from the bloodstream into the brain tissue.
Claudin-5 is a major component of the tight junctions in the BBB, which accounts for its low permeability. This strict regulation protects the nervous system from circulating toxins, pathogens, and hormone fluctuations that could interfere with neural function. Only small, lipid-soluble substances or those with specific transporters can cross the BBB, usually via transcellular transport.
The Blood-Testis Barrier (BTB) is another selective barrier, formed by TJs between adjacent epithelial Sertoli cells. This barrier divides the seminiferous tubule into two compartments, isolating developing germ cells from the systemic blood supply. This isolation maintains a unique fluid composition for sperm development and shields post-meiotic cells from the immune system, which would otherwise recognize them as foreign.
Specialized Roles in Maintaining Fluid Compartments
TJs play a specialized role in organs that must maintain specific fluid compositions and electrochemical gradients. In the kidney, TJs are dynamic along the renal tubules, regulating the reabsorption and secretion of ions and water during urine formation. For example, TJs in the proximal tubule are relatively “leaky,” allowing paracellular reabsorption of major ions like sodium, calcium, and magnesium into the bloodstream.
In the thick ascending limb of the loop of Henle, TJs contain claudin-16, which facilitates the selective movement of calcium and magnesium ions. This finely tuned permeability maintains the body’s mineral balance. The ability of TJs to act as selective ion channels, rather than absolute seals, allows the kidney to adjust the final composition of urine based on physiological needs.
The inner ear relies on TJs to maintain the distinct fluid compartments necessary for hearing and balance. TJs in the cochlea maintain the unique ion concentrations of endolymph, which is high in potassium, and perilymph, which is high in sodium. This separation is essential for generating the endocochlear potential, the electrical driving force that allows sound-detecting hair cells to function. A failure of these specialized TJs can lead to an imbalance of these fluids, resulting in hearing loss or balance disorders.