Regulation of Tight Junction by Cadherin Adhesion and Its Implication in Inflammation and Cancer

Epithelial cells interact with their cellular microenvironment through the forma-tion of different interactions between the plasma membrane-localized receptors of adjacent cells and the extracellular matrix. Of these interactions, tight junctions (TJs), also known as zonula occludens, are the semipermeable intercellular adhesion complexes that control both epithelial and endothelial paracellular permeability preventing the intermixing of apical and basolateral membrane components and, as a result, give rise to morphologically and functionally distinct apical and basolateral domains, leading to epithelial cell polarization. TJ-associated transmembrane proteins, such as occludin, claudins, and junctional adhesion molecules (JAM), encompass an extracellular domain that forms dis-tinct branched strands at the core of the tight junction structure, whereas periph-eral membrane protein, such as zonula occludens-1 (ZO-1), interacts with the transmembrane proteins and aids in their anchoring to the cytoskeleton. Func-tionally, TJs are involved in bidirectional signaling between adhering cells that regulate cellular differentiation, migration, proliferation, and survival enabling them to play a vital role in a number of physiological processes such as innate immunity, aside from the barrier function in the epithelial tissue and mutations in TJ proteins can result in different diseases including cancers, infections, and allergies. Interestingly, TJs have been found to interact with cadherin-based adherens junctions (AJs) and desmosomes that can fine-tune their assembly as well as signaling activities. In this chapter, we discuss the structure and function.