Barriers built on claudins

Abstract

We wish to correct some errors that we inadvertently introduced in revising and editing our recent Commentary. In the text, we incorrectly cited (Wolburg et al., 2003) in reference to the downregulation of claudin-23 in gastric cancer; the reference should be (Katoh and Katoh, 2003) as correctly cited in Table 3. (Peacock et al., 1997) was mistakenly inserted in relation to the discussion of the number of claudin genes. We also wrote the number of human claudin genes as 24, the number currently ascribed to the mouse claudin genes (GenBank). The correct number ascribed to human claudin genes by (Katoh and Katoh, 2003) is 23, up from the originally predicted 20 (Venter et al., 2001). In this regard, it is worth noting that, since our Commentary was published, (Loh et al., 2004) have annotated the claudins in the teleost Fugu rubripes genome and reported 56 claudin genes, of which only 35 can be assigned orthology to 17 mammalian claudin genes, with the remaining 21 being specific to the fish lineage and most of the 56 expressed in a more or less tissue-specific fashion, or at particular developmental stages. This, along with other issues we raised, suggests that additional annotation of multiple other genomes and other functional genomics approaches will be useful to advance our understanding of claudin biology and physiology. Finally, based on a Clustal analysis of full-length claudins, we reported that there is a highly conserved WWCC motif of unknown function within the first loop of the claudins analysed; a motif also reported in alignments of claudins carried out by (Katoh and Katoh, 2003). IntroductionIn multicellular organisms, certain tissues must be separated from each other and protected against the external environment. Epithelial and endothelial sheets achieve this by providing cellular borders that cover external and internal surfaces throughout the body. Complexes between adjacent cells in these sheets include gap junctions, desmosomes, adherence junctions and tight junctions (TJs) -also known as the zonula occludens. Early ultrastructural and morphological data revealed TJs as continuous circumferential intercellular contacts between epithelial cells (Farquhar and Palade, 1963) that create a barrier to the paracellular movement of water, solutes and immune cells (Madara, 1998;Nusrat et al., 2000). Later work showed that this epithelial barrier is heterogeneous in tightness and dynamics depending on the tissue. In addition it is physiologically regulated, and its disruption contributes to human disease. Numerous in-depth reviews on TJs exist (Begley and Brightman, 2003;Fanning et al., 1999; GonzalezMariscal et al., 2003;Heiskala et al., 2001;Madara, 1989;Mitic and Anderson, 1998;Stevenson, 1999;Tsukita and Furuse, 2000a;Tsukita and Furuse, 2000b;Tsukita et al., 2001;Zahraoui et al., 2000). Here we therefore only briefly summarize their essential features and then focus on the recent identification of claudins and our evolving understanding of their contribution to TJ structure and function. Tight...

Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes

“…In normal epithelia, tight junctions provide a critical barrier function between adjacent cells by creating a tight seal that regulates the paracellular movement of water, solutes and macromolecules (Turksen and Troy, 2004). The loss of tight-junctional components is frequently observed in epithelial-derived cancers and disruption of cell-cell adhesions correlates with breast cancer progression, invasion and metastasis (Martin et al, 2004;Osanai et al, 2006;Naik et al, 2008).…”

“…The loss of tight-junctional components is frequently observed in epithelial-derived cancers and disruption of cell-cell adhesions correlates with breast cancer progression, invasion and metastasis (Martin et al, 2004;Osanai et al, 2006;Naik et al, 2008). Claudins are key transmembrane proteins within the tight junction complex that participate in homo-and heterotypic interactions between adjacent cells (Turksen and Troy, 2004). Potential roles for claudin proteins in breast cancer progression are complex.…”

Prostaglandin E2 Produced by Entamoeba histolytica Signals via EP4 Receptor and Alters Claudin-4 to Increase Ion Permeability of Tight Junctions

“…24 -26 Among the 40 different proteins that constitute the TJ complex, the claudin family is responsible for ion barrier maintenance of the paracellular space. 27,28 We speculate that PGE 2 secreted by E. histolytica breaks the TJ ion barrier by selectively altering claudin family members, allowing free paracellular permeability to sodium ions. Any alteration in the TJ ion barrier will markedly affect epithelial transport mechanisms associated with electrolyte and water imbalance.…”

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

“…1 Claudins are integral membrane proteins that have, similar to occludin, four transmembrane domains and two extracellular loops. 6,7 However, unlike occludin, the first loop is longer than the second one. 8 Claudins were named after the latin verb 'claudere', which means 'to close', reflecting their role in tight junctions: they are the key proteins for the sealing of the extracellular space.…”