Occludin and claudins in tight-junction strands: leading or supporting players?

doi:10.1016/S0962-8924(99)01578-0

Trends in Cell Biology

Volume 9, Issue 7, 1 July 1999, Pages 268-273

https://doi.org/10.1016/S0962-8924(99)01578-0 Get rights and content

Abstract

Tight junctions have attracted much interest from cell biologists, especially electron microscopists, since on freeze–fracture electron microscopy they appear as a well-developed network of continuous, anastomosing intramembranous strands (tight-junction strands). These strands might be directly involved in the ‘barrier’ as well as ‘fence’ functions in epithelial and endothelial cell sheets, but until recently little was known of their constituents. This review discusses current understanding of the molecular architecture of tight-junction strands, focusing on the recent discovery of two distinct types of tight-junction-specific integral membrane proteins, occludin and claudins.

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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Trends in Cell Biology

ReviewOccludin and claudins in tight-junction strands: leading or supporting players?

Abstract

Section snippets

Occludin is a component of TJ strands

Claudins and an emerging new gene family

Molecular architecture of TJ strands

Perspective

Acknowledgements

Int. Rev. Cytol.

Cell

Biochim. Biophys. Acta

Genomics

Cell

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Cell

Trends Cell Biol.

Am. J. Physiol.

J. Cell Biol.

J. Cell Biol.

Nature

J. Cell Biol.

J. Cell Biol.

J. Cell Biol.

J. Cell Sci.

J. Cell Sci.

J. Cell Biol.

J. Cell Sci.

J. Cell Biol.

Review
Occludin and claudins in tight-junction strands: leading or supporting players?