Sterol biosensor reveals LAM-family Ltc1-dependent sterol flow to endosomes upon Arp2/3 inhibition.

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Version: Final published version
License: All rights reserved
Serval ID
serval:BIB_6D940CF0A59D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sterol biosensor reveals LAM-family Ltc1-dependent sterol flow to endosomes upon Arp2/3 inhibition.
Journal
The Journal of cell biology
Author(s)
Marek M., Vincenzetti V., Martin S.G.
ISSN
1540-8140 (Electronic)
ISSN-L
0021-9525
Publication state
Published
Issued date
01/06/2020
Peer-reviewed
Oui
Volume
219
Number
6
Pages
e202001147
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Sterols are crucial components of biological membranes, which are synthetized in the ER and accumulate in the plasma membrane (PM). Here, by applying a genetically encoded sterol biosensor (D4H), we visualize a sterol flow between PM and endosomes in the fission yeast Schizosaccharomyces pombe. Using time-lapse and correlative light-electron microscopy, we found that inhibition of Arp2/3-dependent F-actin assembly promotes the reversible relocalization of D4H from the PM to internal sterol-rich compartments (STRIC) labeled by synaptobrevin Syb1. Retrograde sterol internalization to STRIC is independent of endocytosis or an intact Golgi, but depends on Ltc1, a LAM/StARkin-family protein localized to ER-PM contact sites. The PM in ltc1Δ cells over-accumulates sterols and upon Arp2/3 inhibition forms extended ER-interacting invaginations, indicating that sterol transfer contributes to PM size homeostasis. Anterograde sterol movement from STRIC is independent of canonical vesicular trafficking but requires Arp2/3, suggesting a novel role for this complex. Thus, transfer routes orthogonal to vesicular trafficking govern the flow of sterols in the cell.
Keywords
Actin-Related Protein 2-3 Complex/antagonists & inhibitors, Actin-Related Protein 2-3 Complex/metabolism, Actins/metabolism, Antiporters/genetics, Antiporters/metabolism, Biosensing Techniques, Cell Membrane/drug effects, Cell Membrane/genetics, Cell Membrane/metabolism, Endocytosis/drug effects, Endocytosis/genetics, Endoplasmic Reticulum/genetics, Endoplasmic Reticulum/metabolism, Endosomes/drug effects, Endosomes/metabolism, Endosomes/ultrastructure, Genes, Reporter, Golgi Apparatus/metabolism, Microscopy, Electron, Transmission, Mixed Function Oxygenases/genetics, Mixed Function Oxygenases/metabolism, Mutation, R-SNARE Proteins/metabolism, Schizosaccharomyces/metabolism, Sterols/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
25/04/2020 17:15
Last modification date
03/04/2021 5:31
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