ArticleProceedings of the National Academy of Sciences of the United States of America2025
A cell-based scrambling assay reveals the phospholipid headgroup preference of TMEM16F on the plasma membrane.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Lipid flip-flop in biological membranes: through the lens of TMEM16F.Physiological reviews · 2027Review
- Recent advances in TMEM16F: structural plasticity, functional versatility, and implications for human diseases.Cell communication and signaling : CCS · 2026Review
- Integrated analysis of fecal microbiome and serum metabolome reveals the profiling of gut microbiota-related metabolites in rats and mice subjected to prolonged exposure to a high-humidity environment.Frontiers in cellular and infection microbiology · 2026Article
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Abstract
The asymmetric resting distribution of the three major phospholipid classes on the mammalian plasma membrane, with phosphatidylserine and phosphatidylethanolamine mostly on the inner leaflet and phosphatidylcholine mostly on the outer leaflet, is maintained by ATP-dependent flippases and floppases that exhibit headgroup selectivity. Upon signaling cues, this asymmetry can be dissipated by various phospholipid scramblases, allowing cells to respond to stimuli and adapt to different physiological contexts. The prevailing view in the field is that phospholipid scramblases on the plasma membrane act without headgroup preference. Here, we report contrary experimental evidence based on a phospholipid scrambling assay that quantifies the fluorescence polarization (FP) of nitrobenzoxadiazole (NBD)-labeled phospholipids for kinetic monitoring of phospholipid scrambling on the plasma membrane of living cells. Our experiments reveal that the plasma membrane-residing calcium-activated phospholipid scramblase TMEM16F preferentially acts on phosphatidylserine and phosphatidylcholine over phosphatidylethanolamine.
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