ClC-5: A chloride channel with multiple roles in renal tubular albumin uptake

Deanne H. Hryciw, Jenny Ekberg, Carol A. Pollock, Philip Poronnik

Research output: Contribution to journalShort surveyResearchpeer-review

35 Citations (Scopus)

Abstract

ClC-5 is a chloride (Cl-) channel expressed in renal tubules and is critical for normal tubular function. Loss of function nonsense or missense mutations in ClC-5 are associated with Dent's disease, a condition in which patients present with low molecular weight (LMW) proteinuria (including albuminuria), hypercalciuria and nephrolithiasis. Several key studies in ClC-5 knockout mice have shown that the proteinuria results from defective tubular reabsorption of proteins. ClC-5 is typically regarded as an intracellular Cl- channel and thus the defect in this receptor-mediated uptake pathway was initially attributed to the failure of the early endosomes to acidify correctly. ClC-5 was postulated to play a key role in transporting the Cl- ions required to compensate for the movement of H+ during endosomal acidification. However, more recent studies suggest additional roles for ClC-5 in the endocytosis of albumin. ClC-5 is now known to be expressed at low levels at the cell surface and appears to be a key component in the assembly of the macromolecular complex involved in protein endocytosis. Furthermore, mutations in ClC-5 affect the trafficking of v-H+-ATPase and result in decreased expression of the albumin receptor megalin/cubulin. Thus, the expression of ClC-5 at the cell surface as well as its presence in endosomes appears to be essential for normal protein uptake by the renal proximal tubule.

Original languageEnglish
Pages (from-to)1036-1042
Number of pages7
JournalInternational Journal of Biochemistry and Cell Biology
Volume38
Issue number7
DOIs
Publication statusPublished - 2006
Externally publishedYes

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Chloride Channels
Albumins
Endosomes
Endocytosis
Kidney
Proteinuria
Albumin Receptors
Dent Disease
Low Density Lipoprotein Receptor-Related Protein-2
Macromolecular Substances
Hypercalciuria
Nephrolithiasis
Proximal Kidney Tubule
Proteins
Albuminuria
Proton-Translocating ATPases
Acidification
Nonsense Codon
Missense Mutation
Knockout Mice

Cite this

Hryciw, Deanne H. ; Ekberg, Jenny ; Pollock, Carol A. ; Poronnik, Philip. / ClC-5 : A chloride channel with multiple roles in renal tubular albumin uptake. In: International Journal of Biochemistry and Cell Biology. 2006 ; Vol. 38, No. 7. pp. 1036-1042.
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ClC-5 : A chloride channel with multiple roles in renal tubular albumin uptake. / Hryciw, Deanne H.; Ekberg, Jenny; Pollock, Carol A.; Poronnik, Philip.

In: International Journal of Biochemistry and Cell Biology, Vol. 38, No. 7, 2006, p. 1036-1042.

Research output: Contribution to journalShort surveyResearchpeer-review

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