Claudin-3 - the "sealing" component of tight junctions

CLDN3 in MCF-7 cells.jpg

Tight junctions are cell-cell contacts formed at the apical-most part of the lateral membrane between polarized cells and are important players in maintaining the homeostasis and the integrity of epithelia and endothelia. Claudin-3 is one of the central components in tight junction complexes.

Tight junctions form a continuous intercellular barrier and function as gates, regulating the selective passage of ions and larger uncharged molecules through the paracellular space across epithelial and endothelial cell layers ( Zihni et al, 2016).

Claudins, a family of transmembrane proteins consisting of more than 20 members, represent key components of tight junctions. Interesting detail: the name Claudin is derived from the latin word "claudere", which means "to close" and as one can imagine, it is inspired by the critical role of these proteins in the formation of the tight junction barrier (Angelow et al, 2008).

One characteristic example of the Claudin family is Claudin-3 which is present in many epithelia including skin, lung, kidney and intestine. As we can see in the image of the month, it beautifully localizes on the cell-to-cell junctions of MCF-7 cells, clearly forming a continuous belt-like structure surrounding the cells.

Claudin-3 has actually been characterized as the "sealing" component of the tight junctions as it tightly regulates the flow of ions and uncharged solutes in the paracellular space (Milatz et al, 2010). It is also a central part of the endothelial tight junctions in the central nervous system acting as an important regulator of the blood-brain barrier permeability (Wolburg et al, 2003).

Claudin-3 together with the rest of Claudin proteins, regulate to a large extent the paracellular barrier permeability of epithelia and endothelia and play a crucial role in the establishment and maintenance of cell polarity (Shin et al, 2006). In fact, the number and diversity of claudin proteins that exist is expected if we think that they determine the range of ion selectivity which varies significantly among different epithelia.