TY - JOUR
T1 - An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3
AU - Nykjaer, Anders
AU - Dragun, Duska
AU - Walther, Diego
AU - Vorum, Henrik
AU - Jacobsen, Christian
AU - Herz, Joachim
AU - Melsen, Flemming
AU - Christensen, Erik Ilsoe
AU - Willnow, Thomas E.
N1 - Funding Information:
We thank Linda Jacobsen for generating the DBP peptide sequence; Roger Bouillon and Hugo van Baelen for helpful discussions; and Christian Bönsch, Jørgen Gliemann, and David Russel for critical reading of the manuscript. The studies were funded by grants from the Deutsche Forschungsgemeinschaft, NIH (HL 20948), the Lysgaard, Carlsberg, and Novo Nordic Foundations, the Danish Heart Association, and the Danish Medical Research Council.
PY - 1999/2/19
Y1 - 1999/2/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033582543&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033582543&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)80655-8
DO - 10.1016/S0092-8674(00)80655-8
M3 - Article
C2 - 10052453
AN - SCOPUS:0033582543
SN - 0092-8674
VL - 96
SP - 507
EP - 515
JO - Cell
JF - Cell
IS - 4
ER -