title: 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.affiliation: Department of Cell Biology, University of Aarhus, Aarhus, Denmark. hb@ana.au.dk
authors.forename: H
authors.initials: H
authors.lastname: Birn
authors.forename: J C
authors.initials: JC
authors.lastname: Fyfe
authors.forename: C
authors.initials: C
authors.lastname: Jacobsen
authors.forename: F
authors.initials: F
authors.lastname: Mounier
authors.forename: P J
authors.initials: PJ
authors.lastname: Verroust
authors.forename: H
authors.initials: H
authors.lastname: Orskov
authors.forename: T E
authors.initials: TE
authors.lastname: Willnow
authors.forename: S K
authors.initials: SK
authors.lastname: Moestrup
authors.forename: E I
authors.initials: EI
authors.lastname: Christensen
mesh_terms: D000327:Adsorption; D000418:Albumins / Q000502:physiology*; D000818:Animals; D002846:Chromatography, Affinity; D004285:Dogs; D026541:Heymann Nephritis Antigenic Complex; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000502:physiology*; D020349:Surface Plasmon Resonance
chemical_list: D000418:Albumins; D026541:Heymann Nephritis Antigenic Complex; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor