Opposing effects of apolipoproteins E and C on lipoprotein binding to low density lipoprotein receptor-related protein.
Open accessAbstract
The low density lipoprotein receptor-related protein (LRP) from rat liver membranes binds apoprotein E (apoE)-enriched rabbit beta-migrating very low density lipoproteins (beta-VLDL) in a ligand blotting assay on nitrocellulose membranes. Binding was markedly activated when the beta-VLDL was preincubated with recombinant human apoE-3, native human apoE-3 or E-4, or native rabbit apoE. Human apoE-2, which binds poorly (1-2% of apo E-3 binding) to low density lipoprotein receptors, was approximately 40% as effective as apoE-3 or apoE-4 in binding to LRP. Stimulation of apoE-dependent binding to LRP was blocked by the inclusion of a mixture of human apoC proteins, but not apoA-I or A-II, in the preincubation reaction. High concentrations of apoE did not overcome the apoC inhibition. The effects of apoE and apoC on the ligand blotting assay were paralleled by similar effects in the ability of beta-VLDL to stimulate cholesteryl ester synthesis in mutant human fibroblasts that lack low density lipoprotein receptors. These properties of LRP are consistent with the known effects of apoE and apoC on uptake of chylomicron and very low density lipoprotein remnants in the liver and raise the possibility that LRP functions as a receptor for apoE-enriched forms of these lipoproteins in intact animals.
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LRP1 has little isoform-specific difference in its binding affinity to apoE3 and apoE4.
“LRP1 has little isoform-specific difference in its binding affinity to apoE3 and apoE4 (Kowal et al., 1990; Ruiz et al., 2005).”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Kowal et al., 1990
Previous reports have revealed differential activation of APOE receptors by APOE variants.
“Previous reports have revealed differential activation of APOE receptors by APOE variants, potentially explaining the differential biological impact of these variants7–9.”
From Common germline variants of the human APOE gene modulate melanoma progression and survival (2020) · cites this paper as [8]
APOE2 has been shown to exhibit reduced binding to APOE receptors.
“APOE2 has been shown to exhibit reduced binding to APOE receptors7,8.”
From Common germline variants of the human APOE gene modulate melanoma progression and survival (2020) · cites this paper as [8]
The higher APOE2 expression is likely due to feedback compensation for reduced binding of APOE2 to APOE receptors.
“and is likely due to feedback compensation for reduced binding of APOE2 to APOE receptors (24,25).”
From Apolipoprotein E2 Stimulates Protein Synthesis and Promotes Melanoma Progression and Metastasis (2023) · cites this paper as [25]
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“If the LRP1-mediated effect is the major mechanism, it is unclear how apoE isoforms would exert the differential effects on neurite sprouting, given the fact that LRP1 has little isoformspecific difference in its binding affinity to apoE3 and apoE4 (Kowal et al., 1990; Ruiz et al., 2005).”
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Apolipoprotein E2 Stimulates Protein Synthesis and Promotes Melanoma Progression and Metastasis
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- Authors
- Kowal, R. C., Herz, J., Weisgraber, K. H., Mahley, R. W., Brown, M. S., & Goldstein, J. L.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of California, San Francisco (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1990-06
- Volume
- 265
- Issue
- 18
- Pages
- 10771-10779
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1840979539
- Cited by
- 445
- References
- 1
- Citations by year
- 2025: 4 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 7 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 4 · 2014: 9 · 2013: 2 · 2012: 4
- FWCI
- 35.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-20948, HL-41633, P01HL041633, P01HL020948)
- National Institute of General Medical Sciences (GM-08014, T32GM008014)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- apolipoprotein E, apolipoprotein C, low density lipoprotein receptor-related protein, beta-VLDL, lipoprotein binding, APOE isoforms, APOE ε4, cholesteryl ester synthesis, VLDL remnants, chylomicron remnants, hepatic lipoprotein uptake
- MeSH terms
- Animals, Apolipoproteins A, Apolipoproteins E, Cells, Cultured, Cholesterol Esters, Fibroblasts, Humans, Kinetics, Lipoproteins, VLDL, Male, Protein Binding, Rabbits, Receptors, Immunologic, Receptors, LDL, Recombinant Proteins, Skin, Low Density Lipoprotein Receptor-Related Protein-1
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