Syndecan-1 mediates internalization of apoE-VLDL through a low density lipoprotein receptor-related protein (LRP)-independent, non-clathrin-mediated pathway
Year: 2006
Type: article
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 alpha2macroglobulin 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.
Source: Lipids in Health and Disease
Institution: University of New Mexico
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,990
Funders: National Science Foundation, American Heart Association, National Institutes of Health, Health Sciences Center, University of New Mexico, National Heart, Lung, and Blood Institute, National Cancer Institute, National Center for Research Resources, Division of Molecular and Cellular Biosciences
Awards: A CONFOCAL MICROSCOPE FOR HEALTH SCIENCES RESEARCH, G3266237938, FUNCTIONAL PROTEIN ANALYSIS--A SHARED RESOURCE FOR UNM, G456176394, G5616894240, CELL SURFACE ACTIVITIES IN LIPOPROTEIN CATABOLISM, Rab7 and Accessory Protein Function in Late Endocytosis, ENHANCING MULTIDISCIPLINARY BIOMEDICAL RESEARCH, G6936844236, Zeiss Axiovert 2000 for Live Cell Imaging, G781392673, LSM Scandhead w Meta Detector &405 nm Laser
OpenAlex ID: W2139474887