Claudin-17 forms tight junction channels with distinct anion selectivity
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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.
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