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 journalArticle

743 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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    Nykjaer, A., Dragun, D., Walther, D., Vorum, H., Jacobsen, C., Herz, J., Melsen, F., Christensen, E. I., & Willnow, T. E. (1999). An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell, 96(4), 507-515. https://doi.org/10.1016/S0092-8674(00)80655-8