To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

Genome-wide RNAi screen r… - University of Gothenburg, Sweden Till startsida
Sitemap
To content Read more about how we use cookies on gu.se

Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells

Journal article
Authors J. R. Kraehling
J. H. Chidlow
C. Rajagopal
M. G. Sugiyama
J. W. Fowler
M. Y. Lee
X. Zhang
C. M. Ramírez
E. J. Park
B. Tao
K. Chen
L. Kuruvilla
B. Larriveé
E. Folta-Stogniew
R. Ola
N. Rotllan
W. Zhou
M. W. Nagle
J. Herz
Kevin Jon Williams
A. Eichmann
W. L. Lee
C. Fernández-Hernando
W. C. Sessa
Published in Nature Communications
Volume 7
ISSN 2041-1723
Publication year 2016
Published at Institute of Medicine, Department of Molecular and Clinical Medicine
Language en
Links dx.doi.org/10.1038/ncomms13516
Subject categories Molecular medicine (genetics and pathology), Molecular medicine

Abstract

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.

Page Manager: Webmaster|Last update: 9/11/2012
Share:

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?