ClC-5: Physiological role and biophysical mechanisms

Cell Calcium. 2015 Jul;58(1):57-66. doi: 10.1016/j.ceca.2014.09.007. Epub 2014 Nov 13.

Abstract

Cl(-) transport in animal cells has fundamental physiological roles and it is mediated by a variety of protein families, one of them being the CLC family of ion channels and transporters. Besides their physiological relevance, CLC proteins show peculiar biophysical properties. This review will focus on a member of the CLC protein family, the endosomal Cl(-)/H(+) antiporter ClC-5. ClC-5 mutations cause Dent's disease, a renal syndrome due to defective protein reabsorption in the proximal tubule. This established the critical function of ClC-5 for endocytosis. However, our understanding of ClC-5's molecular role in endosomes and of its biophysical properties has proved elusive in spite of important progress achieved in the last two decades. Early models in which ClC-5 would provide a shunt conductance to enable efficient endosomal acidification conflicted with the antiport activity of ClC-5 that has more recently emerged. Currently, the physiological role of ClC-5 is hotly debated and its biophysical properties are still not fully understood.

Keywords: Chloride transport; Dent's disease; Endocytosis; Endosome; Gating; Transporter.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chloride Channels / chemistry
  • Chloride Channels / genetics
  • Chloride Channels / metabolism*
  • Dent Disease / metabolism
  • Dent Disease / pathology
  • Endosomes / metabolism
  • Humans
  • Ion Transport
  • Protein Structure, Tertiary
  • Vacuolar Proton-Translocating ATPases / chemistry
  • Vacuolar Proton-Translocating ATPases / metabolism

Substances

  • CLC-5 chloride channel
  • Chloride Channels
  • Vacuolar Proton-Translocating ATPases