Tight junction dynamics: Is paracellular transport regulated?

Abstract

The tight junction, or zonula occludens (ZO), is a narrow belt-like structure on the plasma membrane of transporting epithelial cells that circumferentially wraps each cell and adjoinsit with its neighbors. In general, the ZO resides at the apical pole of the cell and separates the apical and basolateral plasma membranes (figure). Focally within this ZO belt, the lateral membranes of adjacent cells closely approximate one another. These sites of intimate contact, colloquially termed membrane “kisses:’ are thought to represent the physical sites at which diffusion of molecules across the ZO is impeded. As viewed en face in replicas of freeze-fractured plasma membranes, the ZO appears as an anastamosing web of strands. These strands represent the kiss sites and thus allow one to trace the course of the kisses along the plane of the lateral membrane (see Gumbiner, Am. J. Physiol. 253, C749-C758, 1987). The ZO has two known functions. First, by helping to restrict specific transporters, pumps, and channels to either the apical or basolateral membrane domains, it assists in-but is not solely responsible for-the maintenance of the surface polarity required for vectorial transepithelial transport processes (e.g., salt absorption). Second, by acting as a diffusion barrier, it helps retain the differences in extracellular fluid composition that exist across epithelia as a result of vectorial transport. There are only two pathways by which molecules can cross the epithelium: the transcellular and the paracellular (figure). The ZO appears to be the rate-limiting barrier that restricts flow through the paracellular pathway. It is now generally agreed that the ZO is a relative. rather than an absolute, barrier. For example, the electrical resistance of epithelia from different tissues can vary by two orders of magnitude, and these differences are thought largely to reflect variations in ZO ion permeability (see Powell, Minireview