Wnt directs the endosomal flux of LDL-derived cholesterol and lipid droplet homeostasis.

Details

Serval ID
serval:BIB_435435BD0282
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Wnt directs the endosomal flux of LDL-derived cholesterol and lipid droplet homeostasis.
Journal
Embo Reports
Author(s)
Scott C.C., Vossio S., Vacca F., Snijder B., Larios J., Schaad O., Guex N., Kuznetsov D., Martin O., Chambon M., Turcatti G., Pelkmans L., Gruenberg J.
ISSN
1469-3178 (Electronic)
ISSN-L
1469-221X
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
16
Number
6
Pages
741-752
Language
english
Abstract
The Wnt pathway, which controls crucial steps of the development and differentiation programs, has been proposed to influence lipid storage and homeostasis. In this paper, using an unbiased strategy based on high-content genome-wide RNAi screens that monitored lipid distribution and amounts, we find that Wnt3a regulates cellular cholesterol. We show that Wnt3a stimulates the production of lipid droplets and that this stimulation strictly depends on endocytosed, LDL-derived cholesterol and on functional early and late endosomes. We also show that Wnt signaling itself controls cholesterol endocytosis and flux along the endosomal pathway, which in turn modulates cellular lipid homeostasis. These results underscore the importance of endosome functions for LD formation and reveal a previously unknown regulatory mechanism of the cellular programs controlling lipid storage and endosome transport under the control of Wnt signaling.
Keywords
Animals, Cell Line, Cholesterol, LDL/genetics, Cholesterol, LDL/metabolism, Endocytosis, Endosomes/metabolism, Epithelial Cells/ultrastructure, Gene Expression Profiling, HeLa Cells, High-Throughput Screening Assays, Homeostasis, Humans, L Cells (Cell Line), Lipid Droplets/metabolism, Mice, Oleic Acid/pharmacology, RNA Interference, Wnt Signaling Pathway, Wnt3A Protein/metabolism
Pubmed
Open Access
Yes
Create date
10/03/2016 19:57
Last modification date
20/08/2019 14:47
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