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J Biol Chem, Vol. 273, Issue 9, 5235-5242, February 27, 1998
From the 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.
The Intrinsic Factor-Vitamin B12 Receptor and Target
of Teratogenic Antibodies Is a Megalin-binding Peripheral Membrane
Protein with Homology to Developmental Proteins
,
,,,,,
Department of Medical Biochemistry,
University of Aarhus, 8000 Aarhus C, Denmark, Institut National
de la Santé et de la Recherche Médicale, U489,
Hôpital Tenon, 75020 Paris, France, ** Tulane University Medical
and Astrobiology Centers and Veterans Affairs Medical Center, New
Orleans, Louisiana 70112, Département
de Biochimie, Hôpital Tenon, 75020 Paris, France, and the
§§ Department of Cell Biology, Institute of
Anatomy, University of Aarhus, 8000 Aarhus C, Denmark
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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S. M. Hammad, S. Stefansson, W. O. Twal, C. J. Drake, P. Fleming, A. Remaley, H. B. Brewer Jr., and W. S. Argraves Cubilin, the endocytic receptor for intrinsic factor-vitamin B12 complex, mediates high-density lipoprotein holoparticle endocytosis PNAS, August 31, 1999; 96(18): 10158 - 10163. [Abstract] [Full Text] [PDF]
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M. Kristiansen, R. Kozyraki, C. Jacobsen, E. Nexo, P. J. Verroust, and S. K. Moestrup Molecular Dissection of the Intrinsic Factor-Vitamin B12 Receptor, Cubilin, Discloses Regions Important for Membrane Association and Ligand Binding J. Biol. Chem., July 16, 1999; 274(29): 20540 - 20544. [Abstract] [Full Text] [PDF]
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A. Lindblom, N. Quadt, T. Marsh, D. Aeschlimann, M. Morgelin, K. Mann, P. Maurer, and M. Paulsson The Intrinsic Factor-Vitamin B12 Receptor, Cubilin, Is Assembled into Trimers via a Coiled-coil alpha -Helix J. Biol. Chem., March 5, 1999; 274(10): 6374 - 6380. [Abstract] [Full Text] [PDF]
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V. Batuman, P. J. Verroust, G. L. Navar, J. H. Kaysen, F. O. Goda, W. C. Campbell, E. Simon, F. Pontillon, M. Lyles, J. Bruno, et al. Myeloma light chains are ligands for cubilin (gp280) Am J Physiol Renal Physiol, August 1, 1998; 275(2): F246 - F254. [Abstract] [Full Text] [PDF]
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R. Kozyraki, M. Kristiansen, A. Silahtaroglu, C. Hansen, C. Jacobsen, N. Tommerup, P. J. Verroust, and S. K. Moestrup The Human Intrinsic Factor-Vitamin B12 Receptor, Cubilin: Molecular Characterization and Chromosomal Mapping of the Gene to 10p Within the Autosomal Recessive Megaloblastic Anemia (MGA1) Region Blood, May 15, 1998; 91(10): 3593 - 3600. [Abstract] [Full Text] [PDF]
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M. M. Sousa, A. G. W. Norden, C. Jacobsen, T. E. Willnow, E. I. Christensen, R. V. Thakker, P. J. Verroust, S. K. Moestrup, and M. J. Saraiva Evidence for the Role of Megalin in Renal Uptake of Transthyretin J. Biol. Chem., December 1, 2000; 275(49): 38176 - 38181. [Abstract] [Full Text] [PDF]
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R. Burmeister, I.-M. Boe, A. Nykjaer, C. Jacobsen, S. K. Moestrup, P. Verroust, E. I. Christensen, J. Lund, and T. E. Willnow A Two-receptor Pathway for Catabolism of Clara Cell Secretory Protein in the Kidney J. Biol. Chem., April 13, 2001; 276(16): 13295 - 13301. [Abstract] [Full Text] [PDF]
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R. R. Yammani, S. Seetharam, and B. Seetharam Identification and Characterization of Two Distinct Ligand Binding Regions of Cubilin J. Biol. Chem., November 21, 2001; 276(48): 44777 - 44784. [Abstract] [Full Text] [PDF]
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R. Kozyraki, J. Fyfe, P. J. Verroust, C. Jacobsen, A. Dautry-Varsat, J. Gburek, T. E. Willnow, E. I. Christensen, and S. K. Moestrup Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia PNAS, October 23, 2001; 98(22): 12491 - 12496. [Abstract] [Full Text] [PDF]
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