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Endocytosis of apolipoprotein A-V by members of the low density lipoprotein receptor and the VPS10p domain receptor families

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Endocytosis of apolipoprotein A-V by members of the low density lipoprotein receptor and the VPS10p domain receptor families. / Nilsson, Stefan K; Christensen, Stine; Raarup, Merete K; Ryan, Robert O; Nielsen, Morten S; Olivecrona, Gunilla.

I: Journal of Biological Chemistry, Bind 283, Nr. 38, 2008, s. 25920-7.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Nilsson, SK, Christensen, S, Raarup, MK, Ryan, RO, Nielsen, MS & 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, bind 283, nr. 38, s. 25920-7. https://doi.org/10.1074/jbc.M802721200

APA

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, 283(38), 25920-7. https://doi.org/10.1074/jbc.M802721200

CBE

Nilsson SK, Christensen S, Raarup MK, Ryan RO, Nielsen MS, 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. 283(38):25920-7. https://doi.org/10.1074/jbc.M802721200

MLA

Vancouver

Nilsson SK, Christensen S, Raarup MK, Ryan RO, Nielsen MS, Olivecrona G. Endocytosis of apolipoprotein A-V by members of the low density lipoprotein receptor and the VPS10p domain receptor families. Journal of Biological Chemistry. 2008;283(38):25920-7. https://doi.org/10.1074/jbc.M802721200

Author

Nilsson, Stefan K ; Christensen, Stine ; Raarup, Merete K ; Ryan, Robert O ; Nielsen, Morten S ; Olivecrona, Gunilla. / Endocytosis of apolipoprotein A-V by members of the low density lipoprotein receptor and the VPS10p domain receptor families. I: Journal of Biological Chemistry. 2008 ; Bind 283, Nr. 38. s. 25920-7.

Bibtex

@article{6a1e51c0fcf211dda987000ea68e967b,
title = "Endocytosis of apolipoprotein A-V by members of the low density lipoprotein receptor and the VPS10p domain receptor families",
abstract = "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.",
keywords = "Animals, Apolipoproteins A, CHO Cells, Cricetinae, Cricetulus, Endocytosis, Golgi Apparatus, Humans, Kidney, LDL-Receptor Related Proteins, Membrane Glycoproteins, Membrane Transport Proteins, Nerve Tissue Proteins, Protein Binding, Protein Structure, Tertiary, Receptors, Cell Surface, Receptors, LDL",
author = "Nilsson, {Stefan K} and Stine Christensen and Raarup, {Merete K} and Ryan, {Robert O} and Nielsen, {Morten S} and Gunilla Olivecrona",
year = "2008",
doi = "10.1074/jbc.M802721200",
language = "English",
volume = "283",
pages = "25920--7",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "38",

}

RIS

TY - JOUR

T1 - Endocytosis of apolipoprotein A-V by members of the low density lipoprotein receptor and the VPS10p domain receptor families

AU - Nilsson, Stefan K

AU - Christensen, Stine

AU - Raarup, Merete K

AU - Ryan, Robert O

AU - Nielsen, Morten S

AU - Olivecrona, Gunilla

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - Animals

KW - Apolipoproteins A

KW - CHO Cells

KW - Cricetinae

KW - Cricetulus

KW - Endocytosis

KW - Golgi Apparatus

KW - Humans

KW - Kidney

KW - LDL-Receptor Related Proteins

KW - Membrane Glycoproteins

KW - Membrane Transport Proteins

KW - Nerve Tissue Proteins

KW - Protein Binding

KW - Protein Structure, Tertiary

KW - Receptors, Cell Surface

KW - Receptors, LDL

U2 - 10.1074/jbc.M802721200

DO - 10.1074/jbc.M802721200

M3 - Journal article

C2 - 18603531

VL - 283

SP - 25920

EP - 25927

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 38

ER -