Lippiat, JD and Smith, AJ (2012) The CLC-5 2Cl-/H+ exchange transporter in endosomal function and Dent's disease. Frontiers in Physiology, 3. 449. ISSN 1664-042X
Abstract
CLC-5 plays a critical role in the process of endocytosis in the proximal tubule of the kidney and mutations that alter protein function are the cause of Dent's I disease. In this X-linked disorder impaired reabsorption results in the wasting of calcium and low molecular weight protein to the urine, kidney stones, and progressive renal failure. Several different ion-transporting and protein clustering roles have been proposed as the physiological function of CLC-5 in endosomal membranes. At the time of its discovery, nearly 20 years ago, it was understandably assumed to be a chloride channel similar to known members of the CLC family, such as CLC-1, suggesting that chloride transport by CLC-5 was critical for endosomal function. Since then CLC-5 was found instead to be a 2Cl-/H+ exchange transporter with voltage-dependent activity. Recent studies have determined that it is this coupled exchange of protons for chloride, and not just chloride transport, which is critical for endosomal and kidney function. This review discusses the recent ideas that describe how CLC-5 might function in endosomal membranes, the aspects that we still do not understand, and where controversies remain.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2012 Lippiat and Smith. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copy right notices concerning any third-party graphics etc. |
Keywords: | Chloride transport; CLC-5; Dent's disease; Endocytosis; Endosomal acidification |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute of Membrane and Systems Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 18 May 2015 11:50 |
Last Modified: | 18 May 2015 11:50 |
Published Version: | http://dx.doi.org/10.3389/fphys.2012.00449 |
Status: | Published |
Publisher: | Frontiers |
Refereed: | Yes |
Identification Number: | 10.3389/fphys.2012.00449 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:84487 |