Endocytosis of Apolipoprotein A-V by Members of the Low Density Lipoprotein Receptor and the Vps10p Domain Receptor Families
| Autor: | Stefan K. Nilsson, Stine Holmegaard Christensen, Robert O. Ryan, Morten Nielsen, Merete K. Raarup, Gunilla Olivecrona |
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| Rok vydání: | 2008 |
| Předmět: |
Endosome
media_common.quotation_subject Golgi Apparatus Nerve Tissue Proteins Receptors Cell Surface Lipids and Lipoproteins: Metabolism Regulation and Signaling CHO Cells Plasma protein binding Biology Kidney Endocytosis Biochemistry Cricetulus Cricetinae polycyclic compounds Animals Humans Internalization Receptor Molecular Biology Apolipoproteins A LDL-Receptor Related Proteins media_common Membrane Glycoproteins Membrane Transport Proteins nutritional and metabolic diseases Cell Biology Ligand (biochemistry) LRP1 Protein Structure Tertiary Cell biology Adaptor Proteins Vesicular Transport Receptors LDL Apolipoprotein A-V LDL receptor lipids (amino acids peptides and proteins) Protein Binding |
| Zdroj: | Nilsson, S K, Christensen, S, Raarup, M K, Ryan, R O, Nielsen, M S & Olivecrona, G 2008, ' Endocytosis of apolipoprotein A-V by members of the low density lipoprotein receptor and the VPS10p domain receptor families ', Journal of Biological Chemistry, vol. 283, no. 38, pp. 25920-7 . https://doi.org/10.1074/jbc.M802721200 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m802721200 |
| Popis: | Udgivelsesdato: 2008-Sep-19 Apolipoprotein A-V (apoA-V) is present in low amounts in plasma and has been found to modulate triacylglycerol levels in humans and in animal models. ApoA-V displays affinity for members of the low density lipoprotein receptor (LDL-R) gene family, known as the classical lipoprotein receptors, including LRP1 and SorLA/LR11. In addition to LDL-A binding repeats, the mosaic receptor SorLA/LR11 also possesses a Vps10p domain. Here we show that apoA-V also binds to sortilin, a receptor from the Vsp10p domain gene family that lacks LDL-A repeats. Binding of apoA-V to sortilin was competed by neurotensin, a ligand that binds specifically to the Vps10p domain. To investigate the biological fate of receptor-bound apoA-V, binding experiments were conducted with cultured human embryonic kidney cells transfected with either SorLA/LR11 or sortilin. Compared with nontransfected cells, apoA-V binding to SorLA/LR11- and sortilin-expressing cells was markedly enhanced. Internalization experiments, live imaging studies, and fluorescence resonance energy transfer analyses demonstrated that labeled apoA-V was rapidly internalized, co-localized with receptors in early endosomes, and followed the receptors through endosomes to the trans-Golgi network. The observed decrease of fluorescence signal intensity as a function of time during live imaging experiments suggested ligand uncoupling in endosomes with subsequent delivery to lysosomes for degradation. This interpretation was supported by experiments with (125)I-labeled apoA-V, demonstrating clear differences in degradation between transfected and nontransfected cells. We conclude that apoA-V binds to receptors possessing LDL-A repeats and Vsp10p domains and that apoA-V is internalized into cells via these receptors. This could be a mechanism by which apoA-V modulates lipoprotein metabolism in vivo. |
| Databáze: | OpenAIRE |
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