Pflügers Archiv - European Journal of Physiology

, Volume 460, Issue 2, pp 543–557

ClC transporters: discoveries and challenges in defining the mechanisms underlying function and regulation of ClC-5

Authors

  • Leigh Wellhauser
    • Department of Biochemistry, Faculty of MedicineUniversity of Toronto
  • Christina D’Antonio
    • Department of Physiology, Faculty of MedicineUniversity of Toronto
    • Department of Biochemistry, Faculty of MedicineUniversity of Toronto
    • Department of Physiology, Faculty of MedicineUniversity of Toronto
    • Programme in Molecular Structure and Function, Research InstituteHospital for Sick Children
Ion Channels, Receptors and Transporters

DOI: 10.1007/s00424-009-0769-5

Cite this article as:
Wellhauser, L., D’Antonio, C. & Bear, C.E. Pflugers Arch - Eur J Physiol (2010) 460: 543. doi:10.1007/s00424-009-0769-5

Abstract

The involvement of several members of the chloride channel (ClC) family of membrane proteins in human disease highlights the need to define the mechanisms underlying their function and the consequences of disease-causing mutations. Despite the utility of high-resolution structural models, our understanding of the molecular basis for function of the chloride channels and transporters in the family remains incomplete. In this review, we focus on recent discoveries regarding molecular mechanisms underlying the regulated chloride:proton antiporter activity of ClC-5, the protein mutated in the Dent’s disease—a kidney disease presenting with proteinuria and renal failure in severe cases. We discuss the putative role of ClC-5 in receptor-mediated endocytosis and protein uptake by the proximal renal tubule and the possible molecular and cellular consequences of disease-causing mutations. However, validation of these models will require future study of the intrinsic function of this transporter, in situ, in the membranes of recycling endosomes in proximal tubule epithelial cells.

Keywords

ChannelsChlorideEpithelial cellIntracellular pHIon transportpH regulation

Copyright information

© Springer-Verlag 2009