ArticleMolecular biology of the cell2018
Phospholipid flippases and Sfk1p, a novel regulator of phospholipid asymmetry, contribute to low permeability of the plasma membrane.
Article in Molecular biology of the cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
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- Cis-unsaturated sphingolipids support growth of sphingoid base-deficient yeast but impair plasma membrane integrity.FEBS open bio · 2025Article
- The Vps13-like protein BLTP2 regulates phosphatidylethanolamine levels to maintain plasma membrane fluidity and breast cancer aggressiveness.Nature cell biology · 2025Article
- Unveiling the genetic basis of the low pH response in the acidophilic yeast Maudiozyma bulderi as a potential host for biorefinery.FEMS yeast research · 2025Article
- Engineering microorganisms for enhanced tolerance to toxic end-products and intermediates.FEMS microbiology reviews · 2025Review
- Visualizing NBD-lipid Uptake in Mammalian Cells by Confocal Microscopy.Bio-protocol · 2023Article
- Alkaliphilic/Alkali-Tolerant Fungi: Molecular, Biochemical, and Biotechnological Aspects.Journal of fungi (Basel, Switzerland) · 2023Review
- Secondary Metabolites Produced by the Blue-Cheese Ripening MoldJournal of fungi (Basel, Switzerland) · 2023Review
- Human lipocalins bind and export fatty acids through the secretory pathway of yeast cells.Frontiers in microbiology · 2023Article
- Loss of tolerance to multiple environmental stresses due to limitation of structural diversity of complex sphingolipids.Molecular biology of the cell · 2022Article
- Tricalbin proteins regulate plasma membrane phospholipid homeostasis.Life science alliance · 2022Article
- A palmitoylation code controls PI4KIIIα complex formation and PI(4,5)P2 homeostasis at the plasma membrane.Journal of cell science · 2022Article
- Marine natural products targeting the eukaryotic cell membrane.The Journal of antibiotics · 2021Review
- Phospholipid flippases and Sfk1 are essential for the retention of ergosterol in the plasma membrane.Molecular biology of the cell · 2021Article
- Proper regulation of inositolphosphorylceramide levels is required for acquirement of low pH resistance in budding yeast.Scientific reports · 2020Article
- Biologically active marine natural products and their molecular targets discovered using a chemical genetics approach.Natural product reports · 2020Review
- DRAM1 regulates autophagy and cell proliferation via inhibition of the phosphoinositide 3-kinase-Akt-mTOR-ribosomal protein S6 pathway.Cell communication and signaling : CCS · 2019Article
- Article
- A systematic approach to identify recycling endocytic cargo depending on the GARP complex.eLife · 2019Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phospholipid flippase (type 4 P-type ATPase) plays a major role in the generation of phospholipid asymmetry in eukaryotic cell membranes. Loss of Lem3p-Dnf1/2p flippases leads to the exposure of phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the cell surface in yeast, resulting in sensitivity to PS- or PE-binding peptides. We isolated Sfk1p, a conserved membrane protein in the TMEM150/FRAG1/DRAM family, as a multicopy suppressor of this sensitivity. Overexpression of SFK1 decreased PS/PE exposure in lem3Δ mutant cells. Consistent with this, lem3Δ sfk1Δ double mutant cells exposed more PS/PE than the lem3Δ mutant. Sfk1p was previously implicated in the regulation of the phosphatidylinositol-4 kinase Stt4p, but the effect of Sfk1p on PS/PE exposure in lem3Δ was independent of Stt4p. Surprisingly, Sfk1p did not facilitate phospholipid flipping but instead repressed it, even under ATP-depleted conditions. We propose that Sfk1p negatively regulates transbilayer movement of phospholipids irrespective of directions. In addition, we showed that the permeability of the plasma membrane was dramatically elevated in the lem3Δ sfk1Δ double mutant in comparison with the corresponding single mutants. Interestingly, total ergosterol was decreased in the lem3Δ sfk1Δ mutant. Our results suggest that phospholipid asymmetry is required for the maintenance of low plasma membrane permeability.
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