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Physiological roles of CLC Cl−/H+ exchangers in renal proximal tubules

  • Ion Channels, Receptors and Transporters
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

The CLC gene family encodes Cl− channels or Cl−/H+ exchangers. While our understanding of their structure–function relationship has greatly benefited from the crystal structure of bacterial homologues, human inherited diseases and knock-out mice were crucial in deciphering their physiological roles. Several vesicular CLC Cl−/H+ exchangers are expressed in the proximal tubule (PT). ClC-5 mutations cause Dent’s disease which is associated with low molecular weight proteinuria and kidney stones. ClC-5 knock-out mice revealed impaired endocytosis as the primary defect in Dent’s disease. It extends to receptor-mediated and fluid-phase endocytosis and entails changes in calciotropic hormones that result in kidney stones. No renal functions could be assigned so far to ClC-3 and ClC-4, which are also expressed in PTs. Loss of ClC-7 or its β-subunit Ostm1 entails lysosomal storage in the PT, in addition to the neuronal lysosomal storage and osteopetrosis that are the hallmarks of ClC-7/Ostm1 loss in mice and men.

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Acknowledgments

We thank EI Christensen for allowing us to reproduce his EM picture in Fig. 3b. Work in our laboratory was supported by the Deutsche Forschungsgemeinschaft, the Bundesministerium für Bildung und Forschung (BMBF) in the framework of the National Genome Project (NGFN2), the European Union, the Prix Louis-Jeantet de Médecine, and the Ernst-Jung-Preis für Medizin to TJJ. VP is supported by Marie Curie Fellowship of the European Union.

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  1. Leibniz-Institut für Molekulare Pharmakologie (FMP) and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Str. 10, 13125, Berlin, Germany

    Vanessa Plans, Gesa Rickheit & Thomas J. Jentsch

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  1. Vanessa Plans
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Correspondence to Thomas J. Jentsch.

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Plans, V., Rickheit, G. & Jentsch, T.J. Physiological roles of CLC Cl−/H+ exchangers in renal proximal tubules. Pflugers Arch - Eur J Physiol 458, 23–37 (2009). https://doi.org/10.1007/s00424-008-0597-z

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