Cited by 105Cholesterol and Lipid MetabolismBarrier Structure and Function StudiesDrug Transport and Resistance Mechanisms

A New Low Density Lipoprotein Receptor Homologue with 8 Ligand Binding Repeats in Brain of Chicken and Mouse

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Novak, Sabine, Hiesberger, Thomas, Schneider, Wolfgang J., Nimpf, Johannes·1996·Journal of Biological Chemistry

Abstract

The blood-brain barrier necessitates disparate macromolecular transport systems in the brain and central nervous system. We now report the discovery of a new member of the low density lipoprotein receptor (LDLR) family whose expression is highly restricted to the brain. The full-length cDNA specifying the chicken receptor (open reading frame, 2754 base pairs) as well as a cDNA for the major portion of its murine homologue have been obtained. The novel receptor shows the greatest similarity to the group of LDLR relatives with 8 ligand binding repeats, in chicken termed LR8 and in mammals, very low density lipoprotein receptors. Thus, in addition to 8 tandemly arranged ligand binding repeats, the five-domain receptor contains an O-linked sugar region and the internalization signal, Phe-Asp-Asn-Pro-Val-Tyr, typical for all LDLR gene family members. In chicken, the 6.5-kb receptor transcript is present at high levels in brain and at much lower levels in extraoocytic cells of the ovary; in mouse, the same transcript of 6.5 kb was detected in brain, but not in heart (the major site of very low density lipoprotein receptor expression), lung, liver, kidney, and ovary. An antibody directed against the predicted carboxyl terminus of the avian receptor detected a 130-kDa protein in brain extracts. The apparent size of the immunoreactive protein is compatible with extensive glycosylation of the 894-residue mature form of the receptor. The presence of this novel receptor in brain of a bird and a rodent suggests an important and evolutionary conserved function.

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  1. Saito, A., Pietromonaco, S., Loo, A. K., and Farquhar, M. G. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 9725-9729
  2. Takahashi, S., Kawarabayasi, Y., Nakai, T., Sakai, J., and Yamamoto, T. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 9252-9256
  3. Willnow, T. E., Rohlmann, A., Horton, J., Otani, H., Braun, J. R., Hammer, R. E., and Herz, J. (1996) EMBO J., in press 13. Bu, G., Geuze, H. J., Strous, G. J., and Schwartz, A. L. (1995) EMBO J. 14, 2269 -2280
  4. Schmechel, D. E., Saunders, A. M., Strittmatter, W. J., Crain, B. J., Hulette, C. M., Joo, S. H., Perciak, V. M., Goldgaber, D., and Roses, A. D. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 9649 -9653

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Authors
Novak, S., Hiesberger, T., Schneider, W. J., & Nimpf, J.
Affiliations
University of Vienna (AT)
Corresponding author
Nimpf, Johannes
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1996-05
Volume
271
Issue
20
Pages
11732-11736
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2076013624
Cited by
105
References
1
Citations by year
2025: 1 · 2024: 3 · 2022: 2 · 2020: 1 · 2018: 2 · 2017: 1 · 2014: 4 · 2013: 2 · 2012: 4
FWCI
16.68
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
low-density lipoprotein receptor family, VLDLR, blood-brain barrier, O-glycosylation, chickens, mice, ovary, receptor evolution
MeSH terms
Amino Acid Sequence, Animals, Base Sequence, Brain Chemistry, Chickens, Female, Ligands, Mice, Inbred BALB C, Molecular Sequence Data, Rabbits, Receptors, LDL, Mice

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