The tight junction: a multifunctional complex

Abstract

Multicellular organisms are separated from the external environment by a layer of epithelial cells whose integrity is maintained by intercellular junctional complexes composed of tight junctions, adherens junctions, and desmosomes, whereas gap junctions provide for intercellular communication. The aim of this review is to present an updated overview of recent developments in the area of tight junction biology. In a relatively short time, our knowledge of the tight junction has evolved from a relatively simple view of it being a permeability barrier in the paracellular space and a fence in the plane of the plasma membrane to one of it acting as a multicomponent, multifunctional complex that is involved in regulating numerous and diverse cell functions. A group of integral membrane proteins-occludin, claudins, and junction adhesion molecules-interact with an increasingly complex array of tight junction plaque proteins not only to regulate paracellular solute and water flux but also to integrate such diverse processes as gene transcription, tumor suppression, cell proliferation, and cell polarity.

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

“…Kidneys are composed of hundreds of thousands of functionally independent units called nephrons, and each nephron independently controls its own permeability and solute transport capabilities by changing its adhesive characteristics on the basis of external signals. The normal function of nephrons highly depends on epithelial cellecell adhesion and the surrounding extracellular matrix, 16,37 and adhesion molecules such as cadherins and integrins are key mediators of adhesion. 38,39 Our data indicate that TMIGD1 regulates kidney epithelial cell permeability because overexpression of TMIGD1 increased TEER and reduced permeability; reducing expression of TMIGD1 abrogated TEER.…”

Gliadin Induces an Increase in Intestinal Permeability and Zonulin Release by Binding to the Chemokine Receptor CXCR3

“…4 Increased intestinal permeability appears to be an early biologic change that precedes the onset of autoimmune diseases, including CD and type I diabetes. 8,23,24 The peculiarity of CD is that it is the only autoimmune disease for which the triggering environmental factor gliadin is known.…”

“…3 Under physiologic conditions, access of gliadin to gutassociated lymphoid tissue is prevented by competent intercellular tight junctions (TJ) that limit passage of macromolecules (including gliadin peptides) across the intestinal epithelial barrier. 4 In susceptible individuals, however, the interplay between the initiating stimulus (eg, gliadin) and intestinal cells triggers TJ disassembly. It has been hypothesized that this is an early biologic change that precedes the onset of gliadin-induced immune events that eventually lead to the pathology associated with CD.…”

Phosphorylation of claudin-4 by PKCε regulates tight junction barrier function in ovarian cancer cells

“…Numerous agents and cell signaling pathways interact with the TJ protein complex [21,22] and the involvement of kinases in the biogenesis and regulation of the TJ components is well established [23][24][25][26][27][28]. Interestingly, several studies have demonstrated the involvement of various kinases in the phosphorylation and regulation of claudin proteins [29][30][31][32][33][34][35][36][37], and we have recently shown that phosphorylation of claudin-3 by PKA can affect TJ properties in ovarian cancer cells [38].…”