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Function and regulation of claudins in the thick ascending limb of Henle

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Abstract

The thick ascending limb (TAL) of Henle mediates transcellular reabsorption of NaCl while generating a lumen-positive voltage that drives passive paracellular reabsorption of divalent cations. Disturbance of paracellular reabsorption leads to Ca2+ and Mg2+ wasting in patients with the rare inherited disorder of familial hypercalciuric hypomagnesemia with nephrocalcinosis (FHHNC). Recent work has shown that the claudin family of tight junction proteins form paracellular pores and determine the ion selectivity of paracellular permeability. Importantly, FHHNC has been found to be caused by mutations in two of these genes, claudin-16 and claudin-19, and mice with knockdown of claudin-16 reproduce many of the features of FHHNC. Here, we review the physiology of TAL ion transport, present the current view of the role and mechanism of claudins in determining paracellular permeability, and discuss the possible pathogenic mechanisms responsible for FHHNC.

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Acknowledgments

Work from our own groups that is cited here was supported by the German Research Foundation grant GU447/11-1 (to D.G.) and the National Institutes of Health grant DK062283 (to A.Y.).

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  1. Department of Clinical Physiology, Charité, Campus Benjamin Franklin, 12200, Berlin, Germany

    Dorothee Günzel

  2. Division of Nephrology, University of Southern California Keck School of Medicine, 2025 Zonal Avenue, RMR 406, Los Angeles, CA, 90089, USA

    Alan S. L. Yu

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Günzel, D., Yu, A.S.L. Function and regulation of claudins in the thick ascending limb of Henle. Pflugers Arch - Eur J Physiol 458, 77–88 (2009). https://doi.org/10.1007/s00424-008-0589-z

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