This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wen, H. Articles by Fox, H. S. Search for Related Content PubMed PubMed Citation Articles by Wen, H. Articles by Fox, H. S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2004, p. 8408-8417, Vol. 24, No. 19
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.19.8408-8417.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Selective Decrease in Paracellular Conductance of Tight Junctions: Role of the First Extracellular Domain of Claudin-5

Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037

Received 3 February 2004/ Returned for modification 17 March 2004/ Accepted 29 June 2004

Claudin-5 is a protein component of many endothelial tight junctions, including those at the blood-brain barrier, a barrier that limits molecular exchanges between the central nervous system and the circulatory system. To test the contribution of claudin-5 to this barrier function of tight junctions, we expressed murine claudin-5 in Madin-Darby canine kidney II cells. The result was a fivefold increase in transepithelial resistance in claudin-5 transductants and a reduction in conductance of monovalent cations. However, the paracellular flux of neither neutral nor charged monosaccharides was significantly changed in claudin-5 transductants compared to controls. Therefore, expression of claudin-5 selectively decreased the permeability to ions. Additionally, site-directed mutations of particular amino acid residues in the first extracellular domain of claudin-5 altered the properties of the tight junctions formed in response to claudin-5 expression. In particular, the conserved cysteines were crucial: mutation of either cysteine abolishted the ability of claudin-5 to increase transepithelial resistance, and mutation of Cys⁶⁴ strikingly increased the paracellular flux of monosaccharides. These new insights into the functions of claudin-5 at the molecular level in tight junctions may account for some aspects of the blood-brain barrier's selective permeability.

This article has been cited by other articles:

• Phillips, B. E., Cancel, L., Tarbell, J. M., Antonetti, D. A. (2008). Occludin Independently Regulates Permeability under Hydrostatic Pressure and Cell Division in Retinal Pigment Epithelial Cells. IOVS 49: 2568-2576 [Abstract] [Full Text]  
• Angelow, S., El-Husseini, R., Kanzawa, S. A., Yu, A. S. L. (2007). Renal localization and function of the tight junction protein, claudin-19. Am. J. Physiol. Renal Physiol. 293: F166-F177 [Abstract] [Full Text]  
• Van Itallie, C. M., Rogan, S., Yu, A., Vidal, L. S., Holmes, J., Anderson, J. M. (2006). Two splice variants of claudin-10 in the kidney create paracellular pores with different ion selectivities. Am. J. Physiol. Renal Physiol. 291: F1288-F1299 [Abstract] [Full Text]  
• Hou, J., Gomes, A. S., Paul, D. L., Goodenough, D. A. (2006). Study of Claudin Function by RNA Interference. J. Biol. Chem. 281: 36117-36123 [Abstract] [Full Text]  
• Hou, J., Paul, D. L., Goodenough, D. A. (2005). Paracellin-1 and the modulation of ion selectivity of tight junctions. J. Cell Sci. 118: 5109-5118 [Abstract] [Full Text]