Cubilin is an albumin binding protein important for renal tubular albumin reabsorption
Henrik Birn, … , Søren K. Moestrup, Erik I. Christensen
Henrik Birn, … , Søren K. Moestrup, Erik I. Christensen
Published May 15, 2000
Citation Information: J Clin Invest. 2000;105(10):1353-1361. https://doi.org/10.1172/JCI8862.
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Article

Cubilin is an albumin binding protein important for renal tubular albumin reabsorption

Abstract

Using affinity chromatography and surface plasmon resonance analysis, we have identified cubilin, a 460-kDa receptor heavily expressed in kidney proximal tubule epithelial cells, as an albumin binding protein. Dogs with a functional defect in cubilin excrete large amounts of albumin in combination with virtually abolished proximal tubule reabsorption, showing the critical role for cubilin in the uptake of albumin by the proximal tubule. Also, by immunoblotting and immunocytochemistry we show that previously identified low–molecular-weight renal albumin binding proteins are fragments of cubilin. In addition, we find that mice lacking the endocytic receptor megalin show altered urinary excretion, and reduced tubular reabsorption, of albumin. Because cubilin has been shown to colocalize and interact with megalin, we propose a mechanism of albumin reabsorption mediated by both of these proteins. This process may prove important for understanding interstitial renal inflammation and fibrosis caused by proximal tubule uptake of an increased load of filtered albumin.

Authors

Henrik Birn, John C. Fyfe, Christian Jacobsen, Francoise Mounier, Pierre J. Verroust, Hans Ørskov, Thomas E. Willnow, Søren K. Moestrup, Erik I. Christensen

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Decreased tubular reabsorption of albumin in megalin-deficient mice. (a ...
Decreased tubular reabsorption of albumin in megalin-deficient mice. (a and b) Immunohistochemistry using an anti-mouse albumin antibody (1:3,000) to identify albumin in the kidney cortex of normal (a) and megalin-deficient (b) mice. In normal mice (a), evidence of reabsorbed and endocytosed albumin in proximal tubules is clear (arrows), whereas no albumin can be identified inside the proximal tubules of megalin-deficient mice (b). ×1,000. Four megalin-deficient and five normal mice were examined, showing the same difference in labeling pattern. (c and d) Immunocytochemical localization of cubilin using an anti-dog cubilin antibody (1:200) in normal (c) and megalin-deficient (d) mice. Cubilin is expressed and normally distributed in the megalin-deficient mice (d) when compared with controls (c); however, the labeling intensity is reduced. ×600.