ArticleThe Journal of biological chemistry2024
A cholesterol switch controls phospholipid scrambling by G protein-coupled receptors.
Article in The Journal of biological chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Lipid flip-flop in biological membranes: through the lens of TMEM16F.Physiological reviews · 2026Review
- Sorting of lysosomal enzyme and autophagy are regulated by the GGA1-induced TGN lipid scrambling.Science advances · 2026Article
- A single-vesicle fluorescence microscopy platform to quantify phospholipid scrambling.Nature structural & molecular biology · 2026Article
- Article
- TMEM63 proteins act as mechanically activated cholesterol modulated lipid scramblases contributing to membrane mechano-resilience.Nature communications · 2026Article
- Article
- A single vesicle fluorescence microscopy platform to quantify phospholipid scrambling.bioRxiv : the preprint server for biology · 2025Article
- Opsins are Phospholipid Scramblases in All Domains of Life.bioRxiv : the preprint server for biology · 2025Article
- TMC1 and TMC2 are cholesterol-dependent scramblases that regulate membrane homeostasis in auditory hair cells.bioRxiv : the preprint server for biology · 2025Article
- Reversible tuning of membrane sterol levels by cyclodextrin in a dialysis setting.Biophysical journal · 2025Article
- Synthetic Lipid Biology.Chemical reviews · 2025Review
- Imaging Single Particle Profiler to Study Nanoscale Bioparticles Using Conventional Confocal Microscopy.Nano letters · 2025Article
- One-Pot Reconstitution of GPCRs into Unilamellar Vesicles for Fluorescence-Based Phospholipid Scramblase Activity Assay.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Control of G protein-coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Molecular characterization of Rft1, an ER membrane protein associated with congenital disorder of glycosylation RFT1-CDG.bioRxiv : the preprint server for biology · 2024Article
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10 authors at 4 institutions in 3 countries.
Funding
Abstract
Class A G protein-coupled receptors (GPCRs), a superfamily of cell membrane signaling receptors, moonlight as constitutively active phospholipid scramblases. The plasma membrane of metazoan cells is replete with GPCRs yet has a strong resting trans-bilayer phospholipid asymmetry, with the signaling lipid phosphatidylserine confined to the cytoplasmic leaflet. To account for the persistence of this lipid asymmetry in the presence of GPCR scramblases, we hypothesized that GPCR-mediated lipid scrambling is regulated by cholesterol, a major constituent of the plasma membrane. We now present a technique whereby synthetic vesicles reconstituted with GPCRs can be supplemented with cholesterol to a level similar to that of the plasma membrane and show that the scramblase activity of two prototypical GPCRs, opsin and the β1-adrenergic receptor, is impaired upon cholesterol loading. Our data suggest that cholesterol acts as a switch, inhibiting scrambling above a receptor-specific threshold concentration to disable GPCR scramblases at the plasma membrane.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.