Claudin-3 acts as a sealing component of the tight junction for ions of either charge and uncharged solutes

Biochim Biophys Acta. 2010 Nov;1798(11):2048-57. doi: 10.1016/j.bbamem.2010.07.014. Epub 2010 Jul 22.


The paracellular barrier of epithelia and endothelia is established by several tight junction proteins including claudin-3. Although claudin-3 is present in many epithelia including skin, lung, kidney, and intestine and in endothelia, its function is unresolved as yet. We therefore characterized claudin-3 by stable transfection of MDCK II kidney tubule cells with human claudin-3 cDNA. Two clone systems were analyzed, exhibiting high or low claudin-2 expression, respectively. Expression of other claudins was unchanged. Ultrastructurally, tight junction strands were changed toward uninterrupted and rounded meshwork loops. Functionally, the paracellular resistance of claudin-3-transfected monolayers was strongly elevated, causing an increase in transepithelial resistance compared to vector controls. Permeabilities for mono- and divalent cations and for anions were decreased. In the high-claudin-2 system, claudin-3 reduced claudin-2-induced cation selectivity, while in the low-claudin-2 system no charge preference was observed, the latter thus reflecting the "intrinsic" action of claudin-3. Furthermore, the passage of the paracellular tracers fluorescein (332Da) and FD-4 (4kDa) was decreased, whereas the permeability to water was not affected. We demonstrate that claudin-3 alters the tight junction meshwork and seals the paracellular pathway against the passage of small ions of either charge and uncharged solutes. Thus, in a kidney model epithelium, claudin-3 acts as a general barrier-forming protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Claudin-3
  • Claudin-4
  • Claudins
  • Dogs
  • Humans
  • Membrane Proteins / physiology*
  • Permeability
  • Tight Junctions / metabolism*
  • Tight Junctions / ultrastructure
  • Transfection
  • Water / chemistry


  • CLDN2 protein, human
  • CLDN3 protein, human
  • CLDN4 protein, human
  • Claudin-3
  • Claudin-4
  • Claudins
  • Membrane Proteins
  • Water