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

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Official URL:https://doi.org/10.1172/JCI8862
PubMed:View item in PubMed
Creators Name:Birn, H. and Fyfe, J.C. and Jacobsen, C. and Mounier, F. and Verroust, P.J. and Orskov, H. and Willnow, T.E. and Moestrup, S.K. and Christensen, E.I.
Journal Title:Journal of Clinical Investigation
Journal Abbreviation:J Clin Invest
Volume:105
Number:10
Page Range:1353-1361
Date:May 2000
Keywords:Adsorption, Albumins, Affinity Chromatography, Heymann Nephritis Antigenic Complex, Immunohistochemistry, Kidney Tubules, Membrane Glycoproteins/genetics/isolation & purification, Biological Models, Protein Binding, Cell Surface Receptors, Surface Plasmon Resonance, Animals, Dogs, Mice, Rats
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.
ISSN:0021-9738
Publisher:American Society for Clinical Investigation (U.S.A.)
Item Type:Article

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