Evidence for an essential role of megalin in transepithelial transport of retinol

Citation
Ei. Christensen et al., Evidence for an essential role of megalin in transepithelial transport of retinol, J AM S NEPH, 10(4), 1999, pp. 685-695
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
ISSN journal
1046-6673 → ACNP
Volume
10
Issue
4
Year of publication
1999
Pages
685 - 695
Database
ISI
SICI code
1046-6673(199904)10:4<685:EFAERO>2.0.ZU;2-#
Abstract
Transepithelial transport of retinol is linked to retinol-binding protein ( RBP), which is taken up and also synthesized in a number of epithelia. By i mmunocytochemistry of human, rat, and mouse renal proximal tubules, a stron g staining in apical endocytic vacuoles, lysosomes, endoplasmic reticulum, Golgi, and basal vesicles was observed, in accordance with luminal endocyti c uptake as well as a constitutive synthesis and basal secretion of REP. An alysis of mice with target disruption of the gene for the major endocytic r eceptor of proximal tubules, megalin, revealed no REP in proximal tubules o f these mice. Western blotting and HPLC of the urine of the megalin-deficie nt mice instead revealed a highly increased urinary excretion of REP and re tinol, demonstrating that glomerular filtered REP-retinol of megalin-defici ent mice escapes uptake by proximal tubules. A direct megalin-mediated upta ke of purified RBP-retinol was indicated by surface plasmon resonance analy sis and uptake in immortalized rat yolk sac cells. Uptake was partially inh ibited by a polyclonal megalin antibody and the receptor-associated protein . The present data show that the absence of REP-binding megalin causes a si gnificantly increased loss of REP and retinol in the urine, demonstrating a crucial role of megalin in vitamin A homeostasis.