An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3

Anders Nykjaer, Duska Dragun, Diego Walther, Henrik Vorum, Christian Jacobsen, Joachim Herz, Flemming Melsen, Erik Ilsoe Christensen, Thomas E. Willnow

Research output: Contribution to journalArticlepeer-review

765 Scopus citations

Abstract

Steroid hormones may enter cells by diffusion through the plasma membrane. However, we demonstrate here that some steroid hormones are taken up by receptor-mediated endocytosis of steroid-carrier complexes. We show that 25-(OH) vitamin D3 in complex with its plasma carrier, the vitamin D- binding protein, is filtered through the glomerulus and reabsorbed in the proximal tubules by the endocytic receptor megalin. Endocytosis is required to preserve 25-(OH) vitamin D3 and to deliver to the cells the precursor for generation of 1,25-(OH)2 vitamin D3, a regulator of the calcium metabolism. Megalin(-/-) mice are unable to retrieve the steroid from the glomerular filtrate and develop vitamin D deficiency and bone disease.

Original languageEnglish (US)
Pages (from-to)507-515
Number of pages9
JournalCell
Volume96
Issue number4
DOIs
StatePublished - Feb 19 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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