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Genome-wide RNAi sc...
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Kraehling, J. R.
(author)
Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells
- Article/chapterEnglish2016
Publisher, publication year, extent ...
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2016-11-21
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Springer Science and Business Media LLC,2016
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/248053
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https://gup.ub.gu.se/publication/248053URI
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https://doi.org/10.1038/ncomms13516DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL. © The Author(s) 2016.
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Added entries (persons, corporate bodies, meetings, titles ...)
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Chidlow, J. H.
(author)
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Rajagopal, C.
(author)
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Sugiyama, M. G.
(author)
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Fowler, J. W.
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Lee, M. Y.
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Zhang, X.
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Ramírez, C. M.
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Park, E. J.
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Tao, B.
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Chen, K.
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Kuruvilla, L.
(author)
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Larriveé, B.
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Folta-Stogniew, E.
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Ola, R.
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Rotllan, N.
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Zhou, W.
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Nagle, M. W.
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Herz, J.
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Williams, Kevin Jon,1956Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
(author)
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Eichmann, A.
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Lee, W. L.
(author)
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Fernández-Hernando, C.
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Sessa, W. C.
(author)
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Göteborgs universitetInstitutionen för medicin, avdelningen för molekylär och klinisk medicin
(creator_code:org_t)
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In:Nature Communications: Springer Science and Business Media LLC72041-1723
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- By the author/editor
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Kraehling, J. R.
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Chidlow, J. H.
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Rajagopal, C.
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Sugiyama, M. G.
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Fowler, J. W.
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Lee, M. Y.
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show more...
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Zhang, X.
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Ramírez, C. M.
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Park, E. J.
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Tao, B.
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Chen, K.
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Kuruvilla, L.
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Larriveé, B.
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Folta-Stogniew, ...
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Ola, R.
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Rotllan, N.
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Zhou, W.
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Nagle, M. W.
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Herz, J.
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Williams, Kevin ...
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Eichmann, A.
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Lee, W. L.
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Fernández-Hernan ...
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Sessa, W. C.
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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MEDICAL AND HEAL ...
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University of Gothenburg