ArticleProceedings of the National Academy of Sciences of the United States of America2018
Out-of-the-groove transport of lipids by TMEM16 and GPCR scramblases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 78 citations in OpenAlex.
- Distinct structural mechanisms drive gain-of-function activation of TMEM16E in gnathodiaphyseal dysplasia.Research square · 2026Article
- A single-vesicle fluorescence microscopy platform to quantify phospholipid scrambling.Nature structural & molecular biology · 2026Article
- Calcium dependent activation of the TMEM16F scramblase and ion channel.Nature structural & molecular biology · 2026Article
- Crystallographic data for Pyrococcus furiosus dolichylphosphate mannose synthase suggest that the enzyme could flip its glycolipid product.Scientific reports · 2026Article
- Proposed mechanism for Rft1-mediated scrambling of a dolichol-linked oligosaccharide.bioRxiv : the preprint server for biology · 2025Article
- A single vesicle fluorescence microscopy platform to quantify phospholipid scrambling.bioRxiv : the preprint server for biology · 2025Article
- Mechanism of Phosphatidylserine Lipid Scrambling by Human SERINC3, an HIV-1 Restriction Factor.bioRxiv : the preprint server for biology · 2025Article
- Simulation-based survey of TMEM16 family reveals that robust lipid scrambling requires an open groove.eLife · 2025Article
- TMC1 and TMC2 are cholesterol-dependent scramblases that regulate membrane homeostasis in auditory hair cells.bioRxiv : the preprint server for biology · 2025Article
- Groove architecture controls lipid scrambling in simulations of protein and model systems.bioRxiv : the preprint server for biology · 2025Article
- MprF fromScience advances · 2025Article
- Simulation-based survey of TMEM16 family reveals that robust lipid scrambling requires an open groove.bioRxiv : the preprint server for biology · 2025Article
- Wide-ranging cellular functions of ion channels and lipid scramblases in the structurally related TMC, TMEM16 and TMEM63 families.Nature structural & molecular biology · 2025Review
- Activation of TMEM16E scramblase induces ligand independent growth factor receptor signaling and macropinocytosis for membrane repair.Communications biology · 2025Article
- One-Pot Reconstitution of GPCRs into Unilamellar Vesicles for Fluorescence-Based Phospholipid Scramblase Activity Assay.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Structural basis of closed groove scrambling by a TMEM16 protein.Nature structural & molecular biology · 2024Article
- In or out of the groove? Mechanisms of lipid scrambling by TMEM16 proteins.Cell calcium · 2024Review
- Lipid scrambling is a general feature of protein insertases.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural heterogeneity of the ion and lipid channel TMEM16F.Nature communications · 2024Article
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9 authors at 1 institution in 1 country.
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Abstract
Phospholipid scramblases externalize phosphatidylserine to facilitate numerous physiological processes. Several members of the structurally unrelated TMEM16 and G protein-coupled receptor (GPCR) protein families mediate phospholipid scrambling. The structure of a TMEM16 scramblase shows a membrane-exposed hydrophilic cavity, suggesting that scrambling occurs via the ‟credit-card" mechanism where lipid headgroups permeate through the cavity while their tails remain associated with the membrane core. Here we show that afTMEM16 and opsin, representatives of the TMEM16 and GCPR scramblase families, transport phospholipids with polyethylene glycol headgroups whose globular dimensions are much larger than the width of the cavity. This suggests that transport of these large headgroups occurs outside rather than within the cavity. These large lipids are scrambled at rates comparable to those of normal phospholipids and their presence in the reconstituted vesicles promotes scrambling of normal phospholipids. This suggests that both large and small phospholipids can move outside the cavity. We propose that the conformational rearrangements underlying TMEM16- and GPCR-mediated credit-card scrambling locally deform the membrane to allow transbilayer lipid translocation outside the cavity and that both mechanisms underlie transport of normal phospholipids.
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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.