Endocytosis of Intestinal Tight Junction Proteins: In Time and Space

Eukaryotic cells take up macromolecules and particles from the surrounding milieu and also internalize membrane proteins via a precise process of endocytosis. The role of endocytosis in diverse physiological processes such as cell adhesion, cell signaling, tissue remodeling, and healing is well recognized. The epithelial tight junctions (TJs), present at the apical lateral membrane, play a key role in cell adhesion and regulation of paracellular pathway. These vital functions of the TJ are achieved through the dynamic regulation of the presence of pore and barrier-forming proteins within the TJ complex on the plasma membrane. In response to various intracellular and extracellular clues, the TJ complexes are actively regulated by intracellular trafficking. The intracellular trafficking consists of endocytosis and recycling cargos to the plasma membrane or targeting them to the lysosomes for degradation. Increased intestinal TJ permeability is a pathological factor in inflammatory bowel disease (IBD), and the TJ permeability could be increased due to the altered endocytosis or recycling of TJ proteins. This review discusses the current information on endocytosis of intestinal epithelial TJ proteins. The knowledge of the endocytic regulation of the epithelial TJ barrier will provide further understanding of pathogenesis and potential targets for IBD and a wide variety of human disease conditions.