Tight junction proteins

Abstract

A fundamental function of epithelia and endothelia is to separate different compartments within the organism and to regulate the exchange of substances between them. The tight junction (TJ) constitutes the barrier both to the passage of ions and molecules through the paracellular pathway and to the movement of proteins and lipids between the apical and the basolateral domains of the plasma membrane. In recent years more than 40 different proteins have been discovered to be located at the TJs of epithelia, endothelia and myelinated cells. This unprecedented expansion of information has changed our view of TJs from merely a paracellular barrier to a complex structure involved in signaling cascades that control cell growth and differentiation. Both cortical and transmembrane proteins integrate TJs. Among the former are scaffolding proteins containing PDZ domains, tumor suppressors, transcription factors and proteins involved in vesicle transport. To date two components of the TJ filaments have been identified: occludin and claudin. The latter is a protein family with more than 20 members. Both occludin and claudins are integral proteins capable of interacting adhesively with complementary molecules on adjacent cells and of co-polymerizing laterally. These advancements in the knowledge of the molecular structure of TJ support previous physiological models that exhibited TJ as dynamic structures that present distinct permeability and morphological characteristics in different tissues and in response to changing natural, pathological or experimental conditions.

The impact of CLAUDIN-1 on follicular thyroid carcinoma aggressiveness

“…From the currently known 27 CLAU-DIN members, CLAUDIN-1 is assumed to be the most important protein responsible for the paracellular barrier integrity of epithelial cells (Gonzalez-Mariscal et al 2003). In tumor progression, tight junction assembly is often disrupted resulting in the loss of cell membrane localized tight junction proteins (Resnick et al 2005, Tokes et al 2005.…”

Tight junctions in thyroid carcinogenesis: diverse expression of claudin-1, claudin-4, claudin-7 and occludin in thyroid neoplasms

“…In addition, tight junctions block the free diffusion of proteins and lipids between the apical and basolateral domains of the plasma membrane, therefore maintaining cell polarity (fence function). 1,2 Tight junctions are composed of transmembrane and cytoplasmic protein complexes and appear on electron micrographs as series of fusion points between the outer leaflets of plasma membranes of adjacent cells. At these so-called 'kissing points', the intercellular space is eliminated remarkably.…”

“…2,3 Up to now, three groups of macromolecules are considered as bona fide integral components of tight junctions: occludin, claudins and junctional adhesion molecule. 2,4 Occludin represents the first transmembrane protein of tight junctions that was identified and is a 65 kDa protein that spans the membrane four times, thus having two extracellular loops. 5 The cytoplasmic N-and C-terminal domains contain several phosphorylation sites and interact with various proteins.…”

“…5 The cytoplasmic N-and C-terminal domains contain several phosphorylation sites and interact with various proteins. 1,2 The exact role of occludin in tight junctions function is unclear, although a regulatory function is speculated. 1 Claudins are integral membrane proteins that have, similar to occludin, four transmembrane domains and two extracellular loops.…”

“…Different claudins are found at the tight junction of diverse epithelial cells, 11 and this accounts for the observed differences in permeability and electrical resistance of various epithelia. 2,8,10 Previous studies have shown that occludin and claudin-1, -4 and -7 are deregulated in a variety of malignancies; for example, loss of occludin expression or upregulation of claudin-3 and -4 accompanies the progression of endometrial carcinoma, 12,13 reduced expression of claudin-1 correlates with poorer differentiation, disease recurrence and poor survival in stage II colonic cancer, 14 claudin-7 expression has been found reduced in mammary, 15 esophageal, 16 and head and neck carcinomas, 17 whereas claudin-4 overexpression decreases the invasiveness and metastatic potential of pancreatic cancer cells. 18 On the other hand, various cancers (ie ovarian, colon, cervical cancer) are associated with elevated tight junctions proteins expression levels or protein dislocation to the cytoplasm.…”