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Disruption of clc-5 leads to a redistribution of annexin A2 and promotes calcium crystal agglomeration in collecting duct epithelial cells

Lookup NU author(s): Dr Georgina Carr, Professor Nicholas Simmons, Professor John Sayer

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Abstract

Mutations in CLCN5, which encodes the voltage-dependent Cl-/H +antiporter, CLC-5, cause Dent's disease. This disorder is characterized by low molecular-weight proteinuria, hypercalciuria, nephrocalcinosis and nephrolithiasis. Using a collecting duct cell model (mIMCD-3) in which endogenous clc-5 is disrupted by antisense clc-5 or overexpression of truncated clc-5, we demonstrate altered expression of the crystal adhesion molecule, annexin A2. Endogenously expressed annexin A2 is intracellular with limited plasma membrane localization. Following clc-5 disruption, there is both a marked increase in plasma membrane annexin A2 and an increase in cell surface crystal retention and agglomeration, which may be attenuated using pretreatment with anti-annexin A2 antibodies or wheat germ agglutinin lectin but not by concanavalin A. We hypothesize that in Dent's disease, endocytic failure leads to an accumulation at the plasma membrane of crystal-binding molecules that include annexin A2 leading to retention of calcium crystals and ultimately nephrocalcinosis and nephrolithiasis. © Birkhäuser Verlag, 2006.


Publication metadata

Author(s): Carr G, Simmons NL, Sayer JA

Publication type: Article

Publication status: Published

Journal: Cellular and Molecular Life Sciences

Year: 2006

Volume: 63

Issue: 3

Pages: 367-377

ISSN (print): 1420-682X

ISSN (electronic): 1420-9071

Publisher: Birkhaeuser Verlag AG

URL: http://dx.doi.org/10.1007/s00018-005-5510-8

DOI: 10.1007/s00018-005-5510-8

PubMed id: 16429322


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