Physiology and Function of the Tight Junction

Abstract

Understanding of tight junctions has evolved from their historical perception as inert solute barriers to recognition of their physiological and biochemical complexity. Many proteins are specifically localized to tight junctions, including cytoplasmic actin-binding proteins and adhesive transmembrane proteins. Among the latter are claudins, which are critical barrier proteins. Current information suggests that the paracellular barrier is most usefully modeled as having two physiologic components: a system of charge-selective small pores, 4 Å in radius, and a second pathway created by larger discontinuities in the barrier, lacking charge or size discrimination. The first pathway is influenced by claudin expression patterns and the second is likely controlled by different proteins and signals. Recent information on claudin function and disease-causing mutations have led to a more complete understanding of their role in barrier formation, but progress is impeded by lack of high resolution structural information.T ight junctions form the continuous intercellular barrier between epithelial cells, which is required to separate tissue spaces and regulate selective movement of solutes across the epithelium. Although there are now .40 proteins (Schneeberger and Lynch 2004;Yamazaki et al. 2008) identified within the tight junction, the claudin family of transmembrane proteins, named from the Latin claudere to close, has emerged as the most critical for defining tight junction selectivity. Here, we review evidence that claudins regulate permselectivity (including size, electrical resistance, and ionic charge preference) derived from studies in cultured epithelial cell models and the phenotypes of knockout mice and human mutants. We highlight the physiologic relevance of selectivity but only briefly discuss how it might be physiologically regulated and altered in pathologic situations. We develop the perspective that the barrier is usefully described as having two pathways: first a system of charge-selective claudin-based pores that are 4 Å in radius and a second pathway created by larger discontinuities in the barrier and that lacks charge and size discrimination. The two pathways may be controlled by different proteins and signals.

Inhibition of MicroRNA‐155 Supports Endothelial Tight Junction Integrity Following Oxygen‐Glucose Deprivation

“…In contrast to the inhibition of miR‐155, its overexpression did not have a significant effect on the electrical resistance. The electrical resistance of the monolayer is mostly sensitive to the composition of claudins in the TJs 39. Therefore, we suppose that the electrical resistance in OGD/M and OGD/C control cells was similar because of the absence of CLDN1 on the cell membranes in both groups.…”

TMIGD1 Is a Novel Adhesion Molecule That Protects Epithelial Cells from Oxidative Cell Injury

“…29 Overexpression of TMIGD1 in HEK-293 cells increased TEER (Figure 2A), whereas it reduced HEK-293 cell permeability as measured with fluorescently labeled dextran ( Figure 2B). Depleting TMIGD1 in primary human kidney epithelial cells (HK2) by shRNA significantly inhibited TEER ( Figure 2C).…”

Impaired Nutrient Signaling and Body Weight Control in a Na+ Neutral Amino Acid Cotransporter (Slc6a19)-deficient Mouse

“…Permeability of tight junctions is controlled by claudins and occludins (28). To investigate whether the lack of B 0 AT1 had an impact on tight junction permeability, we measured the amount of the tight-junction markers claudin-2 (Cldn2) and occludin (Ocln) by SDS-PAGE Western blotting (Fig.…”