Proteasome analysis of urinary exosomes has identified proteins from all segments of the nephron, including glomerular podocytes (podocin and podocalyxin), proximal tubules (megalin, cubilin
, aquaporin-1, and type IV carbonic anhydrase), thick ascending limb of Henle (type 2 Na-K-2Cl cotransporter), distal convoluted tubule (thiazide-sensitive Na-Cl cotransporter), and the collecting duct (aquaporin 2) (12).
Removal of proteins such as metallothionein, Alb, and A1M from the tubular fluid by endocytosis is mediated by two multiligand receptors: megalin and cubilin
(Christensen et al.
Albumin is reabsorbed via endocytosis mediated by megalin and cubilin
receptors in proximal tubules.
The significance of this finding is that even though the field has known about cubilin
(the protein encoded by CUBN) function from experimental animal studies, our study was the first to establish the link between a genetic variation in this gene and albuminuria," said Linda Kao, senior Johns Hopkins author on the study.
Several proteins mediating iron uptake into cells have been identified, including the ubiquitously expressed transferrin receptor 1, which binds iron complexed to transferrin (31); transferrin receptor 2, the expression of which is restricted to hepatocytes, duodenal crypt cells, and erythroid precursors; divalent metal transporter 1, a H+/divalent metal symporter found in duodenal enterocytes, which mediates uptake of dietary iron (32,33); cubilin
, a protein expressed in polarized epithelial cells in the kidney, which mediates endocytosis of iron and transferrin with its coreceptor megalin (34); and the hemoglobin scavenger receptor CD163, which is expressed on the surface of monocytes and macrophages and receives plasma hemoglobin bound to haptoglobin.
Rat enterocytes secrete SLPs containing alkaline phophatase and cubilin
in response to corn oil feeding.
Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin
in kidney proximal tubules.
Previously, our human recombinant IF was shown to be stable during storage and to have properties comparable to those obtained for human gastric IF in terms of the IF-aquocobalamin spectrum, the relative affinity for cobalamin or the analog cobinamide, and binding to the IF receptor cubilin