Claudin-17 forms tight junction channels with distinct anion selectivity
- 877 Downloads
Barrier properties of tight junctions are determined by the claudin protein family. Many claudins seal this barrier, but others form paracellular channels. Among these, no claudins with general and clear-cut anion selectivity have yet been described, while for claudin-10a and claudin-4, only circumstantial or small anion selectivities have been shown. A claudin with unknown function and tissue distribution is claudin-17. We characterized claudin-17 by overexpression and knock-down in two renal cell lines. Overexpression in MDCK C7 cell layers caused a threefold increase in paracellular anion permeability and switched these cells from cation- to anion-selective. Knockdown in LLC-PK1 cells indorsed the finding of claudin-17-based anion channels. Mutagenesis revealed that claudin-17 anion selectivity critically depends on a positive charge at position 65. Claudin-17 expression was found in two organs: marginal in brain but abundant in kidney, where expression was intense in proximal tubules and gradually decreased towards distal segments. As claudin-17 is predominantly expressed in proximal nephrons, which exhibit substantial, though molecularly not defined, paracellular chloride reabsorption, we suggest that claudin-17 has a unique physiological function in this process. In conclusion, claudin-17 forms channels within tight junctions with distinct anion preference.
KeywordsEpithelium Tight junctions Claudin-17 Permeability Nephron
Distal convoluted tubule
Proximal convoluted tubule
Thin ascending limb of Henle
Thick ascending limb of Henle
We would like to thank In-Fah M. Lee and Detlef Sorgenfrei for their excellent technical assistance. This work was supported by grants of the Deutsche Forschungsgemeinschaft (DFG FOR 721) and the Sonnenfeld-Stiftung Berlin.
Conflict of interest
The authors declare that they have no conflicts of interest.
- 14.Coyne CB, Gambling TM, Boucher RC, Carson JL, Johnson LG (2003) Role of claudin interactions in airway tight junctional permeability. Am J Physiol Lung Cell Mol Physiol 285:1166–1178Google Scholar
- 23.Zeissig S, Bürgel N, Günzel D, Richter JF, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD (2007) Changes in expression and distribution of claudin-2, -5 and -8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Gut 56:61–72PubMedCrossRefGoogle Scholar
- 27.Angelow S, Schneeberger EE, Yu AS (2007) Claudin-8 expression in renal epithelial cells augments the paracellular barrier by replacing endogenous claudin-2. J Membr Biol 215:147–59Google Scholar
- 29.Muto S, Hata M, Taniguchi J, Tsuruoka S, Moriwaki K, Saitou M, Furuse K, Sasaki H, Fujimura A, Imai M, Kusano E, Tsukita S, Furuse M (2010) Claudin-2-deficient mice are defective in the leaky and cation-selective paracellular permeability properties of renal proximal tubules. Proc Natl Acad Sci USA 107:8011–8016PubMedCrossRefGoogle Scholar
- 30.Furuse M, Sasaki H, Tsukita S (1999) Manner of interaction of heterogeneous claudin species within and between tight junction strands. J Cell Biol 147:891–903Google Scholar