PMID- 10052453
OWN - NLM
STAT- MEDLINE
DCOM- 19990318
LR  - 20190705
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 96
IP  - 4
DP  - 1999 Feb 19
TI  - An endocytic pathway essential for renal uptake and activation of the steroid
      25-(OH) vitamin D3.
PG  - 507-15
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.
FAU - Nykjaer, A
AU  - Nykjaer A
AD  - Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany.
FAU - Dragun, D
AU  - Dragun D
FAU - Walther, D
AU  - Walther D
FAU - Vorum, H
AU  - Vorum H
FAU - Jacobsen, C
AU  - Jacobsen C
FAU - Herz, J
AU  - Herz J
FAU - Melsen, F
AU  - Melsen F
FAU - Christensen, E I
AU  - Christensen EI
FAU - Willnow, T E
AU  - Willnow TE
LA  - eng
GR  - R37 HL063762/HL/NHLBI NIH HHS/United States
GR  - HL 20948/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Heymann Nephritis Antigenic Complex)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, LDL)
RN  - 0 (Vitamin D-Binding Protein)
RN  - 1406-16-2 (Vitamin D)
RN  - EC 1.14.- (Steroid Hydroxylases)
RN  - EC 1.14.15.15 (CYP27A1 protein, human)
RN  - EC 1.14.15.15 (Cholestanetriol 26-Monooxygenase)
RN  - EC 1.14.15.15 (Cyp27a1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Bone Development/genetics
MH  - Cholestanetriol 26-Monooxygenase
MH  - Endocytosis/*physiology
MH  - Heymann Nephritis Antigenic Complex
MH  - Humans
MH  - Iodine Radioisotopes
MH  - Kidney Tubules, Proximal/chemistry/*metabolism/ultrastructure
MH  - Membrane Glycoproteins/*genetics/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Microscopy, Electron
MH  - Receptors, LDL/genetics/metabolism
MH  - Steroid Hydroxylases/*pharmacokinetics
MH  - Vitamin D/*metabolism
MH  - Vitamin D Deficiency/genetics/metabolism
MH  - Vitamin D-Binding Protein/urine
EDAT- 1999/03/03 00:00
MHDA- 1999/03/03 00:01
CRDT- 1999/03/03 00:00
PHST- 1999/03/03 00:00 [pubmed]
PHST- 1999/03/03 00:01 [medline]
PHST- 1999/03/03 00:00 [entrez]
AID - S0092-8674(00)80655-8 [pii]
AID - 10.1016/s0092-8674(00)80655-8 [doi]
PST - ppublish
SO  - Cell. 1999 Feb 19;96(4):507-15. doi: 10.1016/s0092-8674(00)80655-8.