- The apical-junctional complex (AJC) is a specialized structure found at the apical region of the lateral membrane in epithelial and endothelial cells, where adjacent cells come into contact.
- It plays a central role in maintaining the integrity, polarity, and barrier function of epithelial tissues.
- The AJC comprises two major intercellular junctions arranged in a vertical sequence: the tight junction (TJ) at the most apical position, and the adherens junction (AJ) located just beneath it. Together, these junctions coordinate to control both cell-cell adhesion and the regulation of paracellular permeability.
- The tight junction forms the outermost seal between neighboring cells and serves as a gatekeeper to restrict the passage of ions, solutes, and macromolecules through the paracellular space. It also plays a critical role in maintaining apical-basal polarity by segregating the apical membrane domain from the basolateral one. Tight junctions are composed of transmembrane proteins such as claudins, occludin, and junctional adhesion molecules (JAMs), which are anchored to the actin cytoskeleton by intracellular scaffold proteins like ZO-1, ZO-2, and ZO-3.
- Located just beneath the tight junction, the adherens junction is primarily responsible for initiating and stabilizing cell-cell adhesion. It is built around the transmembrane protein E-cadherin, which interacts in a calcium-dependent manner with E-cadherins on neighboring cells. The intracellular tail of E-cadherin binds to adaptor proteins including β-catenin, α-catenin, and p120-catenin, which link the junction to the actin cytoskeleton. Beyond mechanical adhesion, adherens junctions also transmit signals that influence cell shape, movement, and differentiation.
- The apical-junctional complex is not exclusive to gastric epithelial cells. Rather, it is a universal feature of all polarized epithelial tissues throughout the body. This includes the intestinal epithelium, renal tubules, airway epithelium, mammary gland ducts, reproductive tract epithelium, and ocular surface epithelia, among others. While the fundamental components are conserved, the specific organization and regulation of the AJC may vary depending on tissue type and physiological demands.
- In the context of infection and disease, the AJC is a common target for microbial pathogens that seek to breach the epithelial barrier. For example, Helicobacter pylori manipulates the AJC of gastric epithelial cells using its effector protein CagA, which binds and mislocalizes key junctional proteins such as ZO-1, JAM-A, and E-cadherin. This leads to compromised barrier function, loss of polarity, and increased susceptibility to inflammation and chronic colonization. Other pathogens such as Shigella, Salmonella, and enteric viruses also target AJC components to facilitate invasion and immune evasion.
- In summary, the apical-junctional complex is a vital structural and functional feature of epithelial cells, ensuring selective permeability, tissue organization, and defense against external threats. Its disruption—whether by pathogens or disease processes—can have profound consequences for tissue integrity and overall health.
