Trends in Cell Biology
ReviewOccludin and claudins in tight-junction strands: leading or supporting players?
Section snippets
Occludin is a component of TJ strands
Occludin is a 60-kDa integral membrane protein that was the first component of TJ strands to be identified9. It was found in the chicken as an antigen for monoclonal antibodies (mAbs) raised against a junctional fraction isolated from chicken liver. After unexpected difficulties, mammalian homologues of occludin were also identified10. Cloning and sequencing of the corresponding cDNAs revealed that occludin has four transmembrane domains, three cytoplasmic domains (long C-terminal and short
Claudins and an emerging new gene family
Claudin-1 and claudin-2 are 23-kDa integral membrane proteins that are structurally related (38% identical at the amino acid sequence level) and were identified recently as the second and third components of TJ strands22. These two proteins also possess four transmembrane domains but do not show any sequence similarity to occludin (Fig. 2). When claudin-1 or -2 was introduced into cultured epithelial cells, these proteins were targeted correctly to and incorporated into pre-existing TJ strands.
Molecular architecture of TJ strands
The question of whether occludin and claudins are the only molecules in the TJ strands remains unsolved. During the course of the identification of claudin-1 and -2 from the isolated junctional fraction, nine integral membrane proteins were found to be enriched in the fraction that contained TJs and adherens junctions22. Among these, only claudin partitioned together with occludin during sonication and sucrose density-gradient centrifugation, suggesting that the other eight integral membrane
Perspective
Judging from the ability to reconstitute TJ strands in L fibroblasts, claudins rather than occludin appear to be the leading players in formation of TJ strands and probably form the major ‘backbone’ of TJ strands. Occludin is an important copolymerizing component, but its function is still open to question. Occludin does not seem to be absolutely essential for TJ formation but it can clearly affect TJ function. A single gene encoding occludin is phylogenetically maintained at least from frogs
Acknowledgements
We thank Kazumasa Morita for helpful discussions and suggestions on the claudin gene family members, and Kazushi Fujimoto for immunoreplica analyses. Our work covered in this review was supported in part by a Grant-in-Aid for Cancer Research and a Grant-in-Aid for Scientific Research (A) from the Ministry of Education, Science and Culture of Japan.
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