Back to Search
Start Over
Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D 3
- Source :
- Proceedings of the National Academy of Sciences. 98:13895-13900
- Publication Year :
- 2001
- Publisher :
- Proceedings of the National Academy of Sciences, 2001.
-
Abstract
- Steroid hormones are central regulators of a variety of biological processes. According to the free hormone hypothesis, steroids enter target cells by passive diffusion. However, recently we demonstrated that 25(OH) vitamin D 3 complexed to its plasma carrier, the vitamin D-binding protein, enters renal proximal tubules by receptor-mediated endocytosis. Knockout mice lacking the endocytic receptor megalin lose 25(OH) vitamin D 3 in the urine and develop bone disease. Here, we report that cubilin, a membrane-associated protein colocalizing with megalin, facilitates the endocytic process by sequestering steroid–carrier complexes on the cellular surface before megalin-mediated internalization of the cubilin-bound ligand. Dogs with an inherited disorder affecting cubilin biosynthesis exhibit abnormal vitamin D metabolism. Similarly, human patients with mutations causing cubilin dysfunction exhibit urinary excretion of 25(OH) vitamin D 3 . This observation identifies spontaneous mutations in an endocytic receptor pathway affecting cellular uptake and metabolism of a steroid hormone.
- Subjects :
- medicine.medical_specialty
Vitamin D-binding protein
medicine.medical_treatment
Endocytic cycle
Receptors, Cell Surface
Biology
Mice
03 medical and health sciences
Dogs
0302 clinical medicine
Internal medicine
medicine
Animals
Humans
Receptor
Calcifediol
030304 developmental biology
0303 health sciences
Multidisciplinary
Vitamin D-Binding Protein
Amnionless
Biological Sciences
LRP2
Cubilin
Hormones
3. Good health
Low Density Lipoprotein Receptor-Related Protein-2
Steroid hormone
Endocrinology
Mutation
030217 neurology & neurosurgery
Hormone
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 98
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....eb17bde720e1765d19d7438f2787688c