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Claudin-17 forms tight junction channels with distinct anion selectivity

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Abstract

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.

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Abbreviations

Cldn:

Claudin

DCT:

Distal convoluted tubule

Occl:

Occludin

PCT:

Proximal convoluted tubule

tAL:

Thin ascending limb of Henle

TAL:

Thick ascending limb of Henle

TJ:

Tight junction

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Acknowledgments

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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Authors and Affiliations

  1. Institute of Clinical Physiology, Campus Benjamin Franklin, Charité, Freie Universität and Humboldt Universität, Hindenburgdamm 30, 12203, Berlin, Germany

    Susanne M. Krug, Dorothee Günzel, Marcel P. Conrad, Rita Rosenthal, Anja Fromm, Salah Amasheh & Michael Fromm

  2. Division of Nutritional Medicine, Department of Gastroenterology, Campus Benjamin Franklin, Charité, Freie Universität and Humboldt Universität, Hindenburgdamm 30, 12203, Berlin, Germany

    Anja Fromm & Jörg D. Schulzke

Authors
  1. Susanne M. Krug
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  2. Dorothee Günzel
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  4. Rita Rosenthal
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Correspondence to Michael Fromm.

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Krug, S.M., Günzel, D., Conrad, M.P. et al. Claudin-17 forms tight junction channels with distinct anion selectivity. Cell. Mol. Life Sci. 69, 2765–2778 (2012). https://doi.org/10.1007/s00018-012-0949-x

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  • DOI: https://doi.org/10.1007/s00018-012-0949-x

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