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

713 Citations (Scopus)

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
StatePublished - Feb 19 1999

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Cholecalciferol
Low Density Lipoprotein Receptor-Related Protein-2
Steroid hormones
Chemical activation
Steroids
Kidney
Endocytosis
Vitamin D-Binding Protein
Hormones
Cell membranes
Deficiency Diseases
Metabolism
Vitamin D
Vitamin D Deficiency
Bone Diseases
Bone
Calcium
Plasmas
Cell Membrane

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Nykjaer, A., Dragun, D., Walther, D., Vorum, H., Jacobsen, C., Herz, J., ... 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.

An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3 . / Nykjaer, Anders; Dragun, Duska; Walther, Diego; Vorum, Henrik; Jacobsen, Christian; Herz, Joachim; Melsen, Flemming; Christensen, Erik Ilsoe; Willnow, Thomas E.

In: Cell, Vol. 96, No. 4, 19.02.1999, p. 507-515.

Research output: Contribution to journalArticle

Nykjaer, A, Dragun, D, Walther, D, Vorum, H, Jacobsen, C, Herz, J, Melsen, F, Christensen, EI & Willnow, TE 1999, 'An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3 ', Cell, vol. 96, no. 4, pp. 507-515.
Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J et al. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3 Cell. 1999 Feb 19;96(4):507-515.
Nykjaer, Anders ; Dragun, Duska ; Walther, Diego ; Vorum, Henrik ; Jacobsen, Christian ; Herz, Joachim ; Melsen, Flemming ; Christensen, Erik Ilsoe ; Willnow, Thomas E. / An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3 In: Cell. 1999 ; Vol. 96, No. 4. pp. 507-515.
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