ORP2 couples LDL-cholesterol transport to FAK activation by endosomal cholesterol/PI(4,5)P-2 exchange

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Takahashi , K , Kanerva , K , Vanharanta , L , Almeida-Souza , L , Lietha , D , Olkkonen , V M & Ikonen , E 2021 , ' ORP2 couples LDL-cholesterol transport to FAK activation by endosomal cholesterol/PI(4,5)P-2 exchange ' , EMBO Journal , vol. 40 , no. 14 , 106871 . https://doi.org/10.15252/embj.2020106871

Title: ORP2 couples LDL-cholesterol transport to FAK activation by endosomal cholesterol/PI(4,5)P-2 exchange
Author: Takahashi, Kohta; Kanerva, Kristiina; Vanharanta, Lauri; Almeida-Souza, Leonardo; Lietha, Daniel; Olkkonen, Vesa M.; Ikonen, Elina
Contributor organization: STEMM - Stem Cells and Metabolism Research Program
Research Programs Unit
Faculty of Medicine
University of Helsinki
Department of Anatomy
Helsinki Institute of Life Science HiLIFE
Institute of Biotechnology
Faculty of Biological and Environmental Sciences
Lipid Trafficking Lab
Date: 2021-07-15
Language: eng
Number of pages: 20
Belongs to series: EMBO Journal
ISSN: 0261-4189
DOI: https://doi.org/10.15252/embj.2020106871
URI: http://hdl.handle.net/10138/335038
Abstract: Low-density lipoprotein (LDL)-cholesterol delivery from late endosomes to the plasma membrane regulates focal adhesion dynamics and cell migration, but the mechanisms controlling it are poorly characterized. Here, we employed auxin-inducible rapid degradation of oxysterol-binding protein-related protein 2 (ORP2/OSBPL2) to show that endogenous ORP2 mediates the transfer of LDL-derived cholesterol from late endosomes to focal adhesion kinase (FAK)-/integrin-positive recycling endosomes in human cells. In vitro, cholesterol enhances membrane association of FAK to PI(4,5)P-2-containing lipid bilayers. In cells, ORP2 stimulates FAK activation and PI(4,5)P-2 generation in endomembranes, enhancing cell adhesion. Moreover, ORP2 increases PI(4,5)P-2 in NPC1-containing late endosomes in a FAK-dependent manner, controlling their tubulovesicular trafficking. Together, these results provide evidence that ORP2 controls FAK activation and LDL-cholesterol plasma membrane delivery by promoting bidirectional cholesterol/PI(4,5)P-2 exchange between late and recycling endosomes.
Subject: cholesterol trafficking
focal adhesion kinase
oxysterol-binding protein-related protein
phosphoinositides
recycling
LOW-DENSITY-LIPOPROTEIN
INTEGRIN ACTIVATION
PLASMA-MEMBRANE
HEARING-LOSS
TRAFFICKING
NPC1
PROTEIN
OSBPL2
COMPLEXES
TRIGGERS
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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