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Cell Mol Life Sci. 2010 Jun;67(12):2131-40. doi: 10.1007/s00018-010-0332-8. Epub 2010 Mar 24.

Participation of the second extracellular loop of claudin-5 in paracellular tightening against ions, small and large molecules.

Author information

1
Leibniz-Institut für Molekulare Pharmakologie, FMP, Robert-Rössle-Str. 10, 13125, Berlin, Germany.

Abstract

Tight junctions control paracellular permeability. Here, we analyzed the impact of residues in the second extracellular loop (ECL2) of mouse claudin-5 on paracellular permeability. Stable expression of claudin-5(wild type) in MDCK-II cells-but not that of mutants R145A, Y148A, Y158A or E159Q-increased transepithelial electrical resistance and decreased fluorescein permeation. Expression of claudin-5(Y148A), (Y158A) or (E159Q) enhanced permeability of FITC-dextran(10 kDa), which was unchanged in cells expressing claudin-5(wild type) or claudin-5(R145A). In contrast, targeting to tight junctions, strand morphology and tight junction assembly were unchanged. It is concluded that R145 is unessential for trans-interaction of claudin-5, but necessary for tightening against small solutes and ions. The highly conserved residues Y148, Y158 and E159 in ECL2 of claudin-5 contribute to homo- and/or heterophilic trans-interaction between classic claudins and thereby tighten the paracellular space against ions, small and large molecules. These results provide novel insights into the molecular function of tight junctions.

PMID:
20333434
DOI:
10.1007/s00018-010-0332-8
[Indexed for MEDLINE]

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