The intrinsic factor-vitamin B12 receptor and target of teratogenic antibodies is a megalin-binding peripheral membrane protein with homology to developmental proteins
| Autor: | Timothy G. Hammond, Mette Kristiansen, J. H. Kaysen, F. O. Goda, Pierre J. Verroust, Erik Ilsø Christensen, Søren K. Moestrup, Didier Brault, F. Pontillon, Hanne H. Rasmussen, Renata Kozyraki |
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| Rok vydání: | 1998 |
| Předmět: |
Receptors
Cell Surface/genetics Intrinsic Factor Kidney Cortex/metabolism Plasma protein binding Biochemistry Kidney Tubules Proximal Teratogens/metabolism Epidermal growth factor 5-HT5A receptor Cloning Molecular Receptor Yolk Sac Membrane Glycoproteins Peripheral membrane protein Membrane Glycoproteins/metabolism DNA Complementary/genetics Immunohistochemistry Vitamin B 12 Epithelial Cells/chemistry Teratogens Bone Morphogenetic Proteins Rabbits Endosomes/chemistry Antibodies/metabolism Protein Binding DNA Complementary Kidney Cortex Molecular Sequence Data Vitamin B 12/metabolism Heymann Nephritis Antigenic Complex Receptors Cell Surface Endosomes Biology Bone Morphogenetic Proteins/genetics Antibodies Epidermal Growth Factor/genetics Cell surface receptor Animals Amino Acid Sequence Molecular Biology Insulin-like growth factor 1 receptor Intrinsic Factor/metabolism Epidermal Growth Factor Sequence Homology Amino Acid Yolk Sac/chemistry Epithelial Cells Cell Biology Kidney Tubules Proximal/chemistry CUB domain Rats Molecular Weight |
| Zdroj: | Moestrup, S K, Kozyraki, R, Madsen, M, Kaysen, J H, Rasmussen, H H, Brault, D, Pontillon, F, Goda, F O, Christensen, E I, Hammond, T G & Verroust, P J 1998, ' The intrinsic factor-vitamin B12 receptor and target of teratogenic antibodies is a megalin-binding peripheral membrane protein with homology to developmental proteins ', The Journal of biological chemistry, vol. 273, no. 9, pp. 5235-42 . https://doi.org/10.1074/jbc.273.9.5235 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.273.9.5235 |
| Popis: | The present report shows the molecular characterization of the rat 460-kDa epithelial glycoprotein that functions as the receptor facilitating uptake of intrinsic factor-vitamin B12 complexes in the intestine and kidney. The same receptor represents also the yolk sac target for teratogenic antibodies causing fetal malformations in rats. Determination of its primary structure by cDNA cloning identified a novel type of peripheral membrane receptor characterized by a cluster of eight epidermal growth factor type domains followed by a cluster of 27 CUB domains. In accordance with the absence of a hydrophobic segment, the receptor could be released from renal cortex membranes by nonenzymatic and nonsolubilizing procedures. The primary structure has no similarity to known endocytic receptors but displays homology to epidermal growth factor and CUB domain proteins involved in fetal development, e.g. the bone morphogenic proteins. Electron microscopic immunogold double labeling of rat yolk sac and renal proximal tubules demonstrated subcellular colocalization with the endocytic receptor megalin, which is expressed in the same epithelia as the 460-kDa receptor. Furthermore, megalin affinity chromatography and surface plasmon resonance analysis revealed a calcium-dependent high affinity binding of the 460-kDa receptor to megalin, which thereby may mediate its vesicular trafficking. Due to the high number of CUB domains, accounting for 88% of the protein mass, we propose the name cubilin for the novel receptor. |
| Databáze: | OpenAIRE |
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