ArticleBiophysical journal2015
Switch-like responses of two cholesterol sensors do not require protein oligomerization in membranes.
Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 82 citations in OpenAlex.
- Visualization of the interaction between sphingomyelin and cholesterol in lipid bilayer membranes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The NaV1.5 auxiliary subunit FGF13 modulates channels by regulating membrane cholesterol independent of channel binding.The Journal of clinical investigation · 2025Article
- T cell cholesterol transport links intestinal immune responses to dietary lipid absorption.Science (New York, N.Y.) · 2025Article
- Lysosomal glucocerebrosidase is needed for ciliary Hedgehog signaling: A convergent pathway contributing to Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Tetraspanin-enriched membrane domains regulate vascular leakage by altering membrane cholesterol accessibility to balance antagonistic GTPases.Nature cardiovascular research · 2025Article
- Nonvesicular cholesterol transport in physiology.The Journal of clinical investigation · 2025Review
- Monitoring Accessible Cholesterol Levels in Immune Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Membrane mechanics dictate axonal pearls-on-a-string morphology and function.Nature neuroscience · 2025Article
- Leishmania protein KMP-11 modulates cholesterol transport and membrane fluidity to facilitate host cell invasion.EMBO reports · 2024Article
- Cholesterol binding to VCAM-1 promotes vascular inflammation.bioRxiv : the preprint server for biology · 2024Article
- Structures of human γδ T cell receptor-CD3 complex.Nature · 2024Article
- Cholesterol trafficking to the ER leads to the activation of CaMKII/JNK/NLRP3 and promotes atherosclerosis.Journal of lipid research · 2024Article
- DGAT2 inhibition blocks SREBP-1 cleavage and improves hepatic steatosis by increasing phosphatidylethanolamine in the ER.Cell metabolism · 2024Article
- A cholesterol-binding bacterial toxin provides a strategy for identifying a specific Scap inhibitor that blocks lipid synthesis in animal cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- 25-Hydroxycholesterol in health and diseases.Journal of lipid research · 2024Review
- Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake.Science (New York, N.Y.) · 2023Article
- Visualization of accessible cholesterol using a GRAM domain-based biosensor.Nature communications · 2023Article
- Regulation of cellular cholesterol distribution via non-vesicular lipid transport at ER-Golgi contact sites.Nature communications · 2023Article
- Decoding the crosstalk between mevalonate metabolism and T cell function.Immunological reviews · 2023Review
- The Inseparable Relationship Between Cholesterol and Hedgehog Signaling.Annual review of biochemistry · 2023Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Many cellular processes are sensitive to levels of cholesterol in specific membranes and show a strongly sigmoidal dependence on membrane composition. The sigmoidal responses of the cholesterol sensors involved in these processes could arise from several mechanisms, including positive cooperativity (protein effects) and limited cholesterol accessibility (membrane effects). Here, we describe a sigmoidal response that arises primarily from membrane effects due to sharp changes in the chemical activity of cholesterol. Our models for eukaryotic membrane-bound cholesterol sensors are soluble bacterial toxins that show an identical switch-like specificity for endoplasmic reticulum membrane cholesterol. We show that truncated versions of these toxins fail to form oligomers but still show sigmoidal binding to cholesterol-containing membranes. The nonlinear response emerges because interactions between bilayer lipids control cholesterol accessibility to toxins in a threshold-like fashion. Around these thresholds, the affinity of toxins for membrane cholesterol varies by >100-fold, generating highly cooperative lipid-dependent responses independently of protein-protein interactions. Such lipid-driven cooperativity may control the sensitivity of many cholesterol-dependent processes.
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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.