Abstract
Without an epidermis, we would be in a sorry state. The epidermal layer not only protects us from environmental pathogens but also acts as a 'barrier' to water loss. The identification of the molecular nature of the barrier has occupied the efforts of skin researchers over many years, with the consensus in the field being that a protein-lipid layer, located in the upper layers of the epidermis, is necessary for establishment and maintenance of a water barrier. Now, evidence has been presented that components of intercellular junctions, termed tight junctions, also play an essential role in development of barrier function in the skin. Remarkably, the data support a hypothesis that was presented more than 30 years ago.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 355-357 |
| Number of pages | 3 |
| Journal | Trends in Cell Biology |
| Volume | 12 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2002 |
Funding
The first integral membrane protein to be identified in the TJ was occludin [11] . Occludin has four hydrophobic transmembrane helices, with both its amino- and carboxy-termini being located in the cytoplasm. ZO-family proteins interact directly with the cytoplasmic domain of occludin [11] . Occludin does not appear essential for TJ assembly as mice in which the gene encoding occludin is genetically disrupted possess TJs and do not suffer any functional loss in barrier function in the intestine [12] . This implies that other integral proteins of the TJ can compensate for the lack of occludin. The best candidates for such compensators are the claudins [13] . The claudins constitute a complex family of molecules that show tissue-specific patterns of expression and probably have independent as well as interdependent functions. Each claudin molecule spans four times through the membrane at the site of the TJ. Remarkably, TJ ‘strands’ can be reconstituted within plasma membranes of cultured fibroblasts by inducing expression of a single claudin gene product, suggesting that claudins are the central building blocks of the TJ [14] . This idea is supported by data from mice lacking claudin-11. In these mutant mice, TJs are absent from myelin sheaths in the central nervous system and Sertoli cells in the testis, with the mice possessing slowed nerve conduction and impaired spermatogenesis [15] . In addition to occludin and claudin, a transmembrane constituent termed junctional adhesion molecule (JAM) localizes to TJs in both epithelial and endothelial cells. JAM belongs to the immunoglobulin superfamily and is believed to have a direct role in the regulation of immune cell transport across cellular monolayers [16] .
ASJC Scopus subject areas
- Cell Biology