Selective decrease in paracellular conductance of tight junctions: Role of the first extracellular domain of claudin-5

Huajie Wen, Debbie D. Watry, M. Cecilia G. Marcondes, Howard S. Fox

Research output: Contribution to journalArticlepeer-review

171 Scopus citations


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 Cys 64 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.

Original languageEnglish (US)
Pages (from-to)8408-8417
Number of pages10
JournalMolecular and cellular biology
Issue number19
StatePublished - Oct 2004
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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