Cited by 276Cholesterol and Lipid MetabolismHeat shock proteins researchCellular transport and secretion

RAP, a specialized chaperone, prevents ligand-induced ER retention and degradation of LDL receptor-related endocytic receptors

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Willnow, T. E., Rohlmann, A., Horton, J., Otani, H., Braun, J. R., Hammer, R. E., Herz, J.·1996·The EMBO Journal

Abstract

The multifunctional low density lipoprotein (LDL) receptor-related protein (LRP) forms a complex with a receptor-associated protein (RAP) within the secretory pathway. RAP inhibits ligand binding to LRP and is required for normal functional expression of LRP in vivo, suggesting a physiological function as a specialized chaperone. We have used RAP-deficient mice, generated by gene targeting, to investigate the role of RAP in the biosynthesis and biological activity of LRP and other members of the LDL receptor gene family in various organs and in embryonic fibroblasts. Our results demonstrate that RAP is required for the proper folding and export of the receptors from the endoplasmic reticulum (ER) by preventing the premature binding of co-expressed ligands. Overexpression of apolipoprotein E (apoE), a high affinity ligand for LRP, results in dramatically reduced cellular LRP expression, an effect that is prevented by co-expression of RAP. RAP thus defines a novel class of molecular chaperones that selectively protect endocytic receptors by binding to newly synthesized receptor polypeptides, thereby preventing ligand-induced aggregation and subsequent degradation in the ER.

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Crossref · 10.1002/j.1460-2075.1996.tb00623.x

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Authors
Willnow, T. E., Rohlmann, A., Horton, J., Otani, H., Braun, J. R., Hammer, R. E., & Herz, J.
Affiliations
The University of Texas Southwestern Medical Center (US)
Venue
The EMBO Journal
Published
1996-06-01
Volume
15
Issue
11
Pages
2632-2639
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W339018046
Cited by
276
References
37
Citations by year
2026: 5 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 6 · 2017: 6 · 2016: 8 · 2015: 9 · 2014: 5 · 2013: 6 · 2012: 4
FWCI
30.81
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
receptor-associated protein, rap, LDL receptor-related protein, LRP, molecular chaperones, endoplasmic reticulum retention, receptor folding, apolipoprotein E, endocytic receptor, secretory pathway, receptor biosynthesis
MeSH terms
Animals, Apolipoproteins E, Cell Compartmentation, Endocytosis, Endoplasmic Reticulum, Ligands, Liver, Membrane Glycoproteins, Microsomes, Liver, Receptors, Immunologic, Receptors, LDL, Mice, Knockout, Molecular Chaperones, Low Density Lipoprotein Receptor-Related Protein-1, Heymann Nephritis Antigenic Complex, Mice

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