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Phospholipid flippases and Sfk1 are essential for the retention of ergosterol in the plasma membrane

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Title: Phospholipid flippases and Sfk1 are essential for the retention of ergosterol in the plasma membrane
Authors: Kishimoto, Takuma Browse this author →KAKEN DB
Mioka, Tetsuo Browse this author
Itoh, Eriko Browse this author
Williams, David E. Browse this author
Andersen, Raymond J. Browse this author
Tanaka, Kazuma Browse this author →KAKEN DB
Issue Date: 15-Jul-2021
Publisher: American Society for Cell Biology
Journal Title: Molecular biology of the cell
Volume: 32
Issue: 15
Start Page: 1374
End Page: 1392
Publisher DOI: 10.1091/mbc.E20-11-0699
Abstract: Sterols are important lipid components of the plasma membrane (PM) in eukaryotic cells, but it is unknown how the PM retains sterols at a high concentration. Phospholipids are asymmetrically distributed in the PM, and phospholipid flippases play an important role in generating this phospholipid asymmetry. Here, we provide evidence that phospholipid flippases are essential for retaining ergosterol in the PM of yeast. A mutant in three flippases, Dnf1-Lem3, Dnf2-Lem3, and Dnf3-Crf1, and a membrane protein, Sfk1, showed a severe growth defect. We recently identified Sfk1 as a PM protein involved in phospholipid asymmetry. The PM of this mutant showed high permeability and low density. Staining with the sterol probe filipin and the expression of a sterol biosensor revealed that ergosterol was not retained in the PM. Instead, ergosterol accumulated in an esterified form in lipid droplets. We propose that ergosterol is retained in the PM by the asymmetrical distribution of phospholipids and the action of Sfk1. Once phospholipid asymmetry is severely disrupted, sterols might be exposed on the cytoplasmic leaflet of the PM and actively transported to the endoplasmic reticulum by sterol transfer proteins.
Type: article
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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