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An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D-3

Official URL:https://doi.org/10.1016/S0092-8674(00)80655-8
PubMed:View item in PubMed
Creators Name:Nykjaer, A. and Dragun, D. and Walther, D. and Vorum, H. and Jacobsen, C. and Herz, J. and Melsen, F. and Christensen, E.I. and Willnow, T.E.
Journal Title:Cell
Journal Abbreviation:Cell
Page Range:507-515
Date:19 February 1999
Keywords:Bone Development, Cholestanetriol 26-Monooxygenase, Electron Microscopy, Endocytosis, Heymann Nephritis Antigenic Complex, Iodine Radioisotopes, LDL Receptors, Membrane Glycoproteins, Proximal Kidney Tubules, Steroid Hydroxylases, Vitamin D, Vitamin D Deficiency, Vitamin D-Binding Protein, Animals, Mice
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.
Publisher:Cell Press (U.S.A.)
Item Type:Article

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