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Cited by 60Proteoglycans and glycosaminoglycans researchCholesterol and Lipid MetabolismLipid metabolism and disorders

Syndecan-1 mediates internalization of apoE-VLDL through a low density lipoprotein receptor-related protein (LRP)-independent, non-clathrin-mediated pathway

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Wilsie, Larissa C, Gonzales, Amanda M, Orlando, Robert A·2006·Lipids in Health and Disease
DOI 10.1186/1476-511x-5-23PMC PMC1592478
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Abstract

Background: Triacylglyerol-rich very low density lipoprotein (VLDL) particles are the primary carriers of fatty acids in the circulation and as such serve as a rich energy source for peripheral tissues. Receptor-mediated uptake of these particles is dependent upon prior association with apolipoprotein E (apoE-VLDL) and is brought about by cell surface heparan sulfate proteoglycans (HSPG) in some cell types and by the low density lipoprotein receptor-related protein (LRP) in others. Although LRP's role in apoE-VLDL uptake has been well studied, the identity of the HSPG family member that mediates apoE-VLDL uptake has not been established. We investigated if syndecan-1 (Syn-1), a transmembrane cell surface HSPG, is able to mediate the internalization of apoE-VLDL and examined the relationship between Syn-1 and LRP toward apoE-VLDL uptake. For this study, we used a human fibroblast cell line (GM00701) that expresses large amounts of LRP, but possesses no LDL receptor activity to eliminate its contributions toward apoE-VLDL uptake. Results: Although LRP in these cells is fully active as established by substantial α 2 macroglobulin binding and internalization, uptake of apoE-VLDL is absent. Expression of human Syn-1 cDNA restored apoE-VLDL binding and uptake by these cells. Competition for this uptake with an LRP ligand-binding antagonist had little or no effect, whereas co-incubation with heparin abolished apoE-VLDL internalization. Depleting Syn-1 expressing cells of K+, to block clathrin-mediated endocytosis, showed no inhibition of Syn-1 internalization of apoE-VLDL. By contrast, treatment of cells with nystatin to inhibit lipid raft function, prevented the uptake of apoE-VLDL by Syn-1. Conclusion: These data demonstrate that Syn-1 is able to mediate apoE-VLDL uptake in human fibroblasts with little or no contribution from LRP and that the endocytic path taken by Syn-1 is clathrin-independent and relies upon lipid raft function. These data are consistent with previous studies demonstrating Syn-1 association with lipid raft domains.

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Authors
Wilsie, L. C., Gonzales, A. M., & Orlando, R. A.
Affiliations
University of New Mexico (US)
Corresponding author
Orlando, Robert A
ORCID
Orlando, Robert A
Venue
Lipids in Health and Disease
Publisher
Springer Science and Business Media LLC
Published
2006-08-31
Volume
5
Issue
1
Pages
23-23
ISSN
1476-511X (ISSN-L)
DOI
10.1186/1476-511x-5-23
PMC
PMC1592478
OpenAlex
W2139474887
Cited by
60
References
62
Citations by year
2026: 2 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 7 · 2013: 8 · 2012: 1
FWCI
1.93
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Lipids in Health and Disease (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Science Foundation (P20 RR11830, S10 RR016918, S10 RR19287, 9982161, S10 RR14668)
  • American Heart Association
  • National Institutes of Health (1s10rr014668-01, 5p20rr011830-03, 1s10rr016918-01)
  • Health Sciences Center, University of New Mexico
  • National Heart, Lung, and Blood Institute (HL 63291, R01HL063291)
  • National Cancer Institute (R24CA088339, R24CA88339)
  • National Center for Research Resources (P20 RR 11830, 1-S10-RR-14668, S10 RR19287, S10 RR-016918, S10RR019287)
  • Division of Molecular and Cellular Biosciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
syndecan-1, apolipoprotein E, VLDL, lipoprotein uptake, heparan sulfate proteoglycans, low density lipoprotein receptor-related protein, clathrin-independent endocytosis, lipid rafts, nystatin, human fibroblasts, heparin
MeSH terms
alpha-Macroglobulins, Animals, Apolipoproteins E, Cell Line, Cells, Cultured, Clathrin, Humans, Lipoproteins, VLDL, Membrane Glycoproteins, Proteoglycans, Rabbits, Low Density Lipoprotein Receptor-Related Protein-1, 3T3-L1 Cells, Mice, Syndecans, Syndecan-1

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