Tight Junction Pore and Leak Pathways: A Dynamic Duo

Abstract

Tissue barriers that restrict passage of liquids, ions, and larger solutes are essential for the development of multicellular organisms. In simple organisms this allows distinct cell types to interface with the external environment. In more complex species, the diversity of cell types capable of forming barriers increases dramatically. Although the plasma membranes of these barrier-forming cells prevent flux of most hydrophilic solutes, the paracellular, or shunt, pathway between cells must also be sealed. This function is accomplished in vertebrates by the zonula occludens, or tight junction. The tight junction barrier is not absolute but is selectively permeable and is able to discriminate between solutes on the basis of size and charge. Many tight junction components have been identified over the past 20 years, and recent progress has provided new insights into the proteins and interactions that regulate structure and function. This review presents these data in a historical context and proposes an integrated model in which dynamic regulation of tight junction protein interactions determines barrier function.

Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium

“…This layer fulfills many critical physiological functions, including mucociliary clearance and innate host defense, and provides a barrier against pathogens and allergens. The luminal cells are highly polarized, and their lateral membranes contain specialized junctional domains that mediate adhesion and the selective transcellular passage of ions, molecules, and immune cells (3). Junctional complexes are connected to the cytoskeleton and form part of an integrated system maintaining epithelial integrity.…”

The Cap1–claudin-4 regulatory pathway is important for renal chloride reabsorption and blood pressure regulation

“…This mechanism is quick (within 1 h) and is exerted extracellularly, making it an attractive strategy for pharmacological intervention at the TJ level. Although the TJ architecture is not resolved, modern imaging approaches have revealed highly dynamic behaviors of the TJ comprising rapid opening/closing events that may reflect constant breaking and establishing of claudin interactions (50). Luminal proteases such as cap1 may contribute to such dynamic behavior of TJ or rely upon the opening event to gain access to its claudin targets.…”

Epidermal tight junctions in health and disease

“…However, it is possible to observe changes in either the TJ ion or macromolecular permeability as an isolated event, independent of each other, 35 because ions and (larger) molecules are likely to use different pathways through the TJ. 36 Therefore, even isolated changes in TER without a change in tracer flux or vice versa may reflect TJ changes. To clearly distinguish between paracellular and transcellular ion permeability, 2-path-impedance can be used (For a review see 34 ).…”