THE TIGHT JUNCTION - STRUCTURE AND FUNCTION

The tight junction (TJ) is a specialized structure that generally circumscribes the most apical region of the lateral plasma membranes of polarized epithelia and endothelia. It apparently consists of two sets of strands, one for each adjacent cell, which seal the lateral intercellular spaces, thus restricting the passage of substances through the paracellular pathway. It also forms a boundary between the apical and basolateral plasma membrane domains. Although polarization of membrane components may proceed independently of the TJ, they apparently segregate certain proteins and lipids into their respective domains, thus preventing their intermixing. The molecular nature of the sealing element is still unknown, but proteins such as ZO-1 and cingulin have recently been isolated and detected in association with the cytoplasmic side of the TJ. A variety of data now suggest that TJ are highly dynamic structures, sensitive to environmental and cellular factors. They are able to control the paracellular pathway depending on physiological requirements, presumably through regulatory mechanisms and interactions with the cytoskeletal microfilament system. Their assembly and sealing may depend on extracellular Ca2+, cell-adhesion mechanisms, recognition and cascades of cellular events yet to be determined. Determination in the near future of the molecular composition of the sealing element in TJ and its control mechanism will undoubtedly contribute to the basic understanding of these important membrane specializations in health and disease.