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Published VersionCC BY V4.0, Open
Journal article
Cofilin Interacts with ClC-5 and Regulates Albumin Uptake in Proximal Tubule Cell Lines
Journal of Biological Chemistry, Vol.278(41), pp.40169-40176
2003
PMID: 12904289
Abstract
Receptor-mediated endocytosis is a constitutive high capacity pathway for the reabsorption of proteins from the glomerular filtrate by the renal proximal tubule. ClC-5 is a voltage-gated chloride channel found in the proximal tubule where it has been shown to be essential for protein uptake, based on evidence from patients with Dent's disease and studies in ClC-5 knockout mice. To further delineate the role of ClC-5 in albumin uptake, we performed a yeast two-hybrid screen with the C-terminal tail of ClC-5 to identify any interactions of the channel with proteins involved in endocytosis. We found that the C-terminal tail of ClC-5 bound the actin depolymerizing protein, cofilin, a result that was confirmed by GST-fusion pulldown assays. In cultured proximal tubule cells, cofilin was distributed in nuclear, cytoplasmic, and microsomal fractions and co-localized with ClC-5. Phosphorylation of cofilin by overexpressing LIM kinase 1 resulted in a stabilization of the actin cytoskeleton. Phosphorylation of cofilin in two proximal tubule cell models (porcine renal proximal tubule and opossum kidney) was also accompanied by a pronounced inhibition of albumin uptake. This study identifies a novel interaction between the C-terminal tail of ClC-5 and cofilin, an actin-associated protein that is crucial in the regulation of albumin uptake by the proximal tubule.
Details
- Title
- Cofilin Interacts with ClC-5 and Regulates Albumin Uptake in Proximal Tubule Cell Lines
- Authors
- Deanne H. Hryciw - The University of QueenslandYinghong Wang - Johns Hopkins UniversityOlivier Devuyst (Author) - UCLouvainCarol A. Pollock - The University of SydneyPhilip Poronnik - The University of QueenslandWilliam B. Guggino (Corresponding Author) - Johns Hopkins University
- Publication details
- Journal of Biological Chemistry, Vol.278(41), pp.40169-40176
- Publisher
- Elsevier Inc.
- Date published
- 2003
- DOI
- 10.1074/jbc.M307890200
- ISSN
- 1083-351X; 0021-9258
- PMID
- 12904289
- Copyright note
- Copyright: © 2003 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.
- Grant note
- This work was funded by National Institutes of Health Grants DK32753 and HL47122 (to W. B. G.), Forton Foundation Grant ARC 00/05-260, Fondation pour la Recherche Scientifique Medicale (to O. D.), the National Health and Medical Research Council of Australia (to C. A. P. and P. P.), and Juvenile Diabetes Foundation International (to P. P. and C. A. P.).
- Organisation Unit
- School of Health - Biomedicine
- Language
- English
- Record Identifier
- 991187230102621
- Output Type
- Journal article
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