Cofilin interacts with ClC-5 and regulates albumin uptake in proximal tubule cell lines

Hryciw, D, Saad, S, Poronnik, P and Pollock, C 2003, 'Cofilin interacts with ClC-5 and regulates albumin uptake in proximal tubule cell lines', Journal of Biological Chemistry, vol. 278, pp. 40169-40176.

Document type: Journal Article
Collection: Journal Articles

Title Cofilin interacts with ClC-5 and regulates albumin uptake in proximal tubule cell lines
Author(s) Hryciw, D
Saad, S
Poronnik, P
Pollock, C
Year 2003
Journal name Journal of Biological Chemistry
Volume number 278
Start page 40169
End page 40176
Total pages 8
Publisher American Society for Biochemistry and Molecular Biology
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.
Subject Biochemistry and Cell Biology not elsewhere classified
Keyword(s) animal cell
cell culture
cell line
chloride channel clc5
controlled study
glomerulus filtration
kidney proximal tubule
kidney tubule absorption
knockout mouse
priority journal
protein binding
protein localization
protein phosphorylation
protein protein interaction
protein transport
two hybrid system
DOI - identifier 10.1074/jbc.M307890200
ISSN 0021-9258
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