ArticleThe Journal of biological chemistry2010
Accessibility of cholesterol in endoplasmic reticulum membranes and activation of SREBP-2 switch abruptly at a common cholesterol threshold.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 108 citations in OpenAlex.
- A dynamic feedback loop between retrograde sterol transport and TORC2 controls adaptation of the plasma membrane to stress.The EMBO journal · 2025Article
- Monitoring Accessible Cholesterol Levels in Immune Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Leishmania protein KMP-11 modulates cholesterol transport and membrane fluidity to facilitate host cell invasion.EMBO reports · 2024Article
- Article
- 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
- A cholesterol switch controls phospholipid scrambling by G protein-coupled receptors.The Journal of biological chemistry · 2024Article
- 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
- The Inseparable Relationship Between Cholesterol and Hedgehog Signaling.Annual review of biochemistry · 2023Review
- A basic model for the association of ligands with membrane cholesterol: application to cytolysin binding.Journal of lipid research · 2023Article
- Chemical potential measurements constrain models of cholesterol-phosphatidylcholine interactions.Biophysical journal · 2023Article
- Cholesterol Transport to the Endoplasmic Reticulum.Cold Spring Harbor perspectives in biology · 2023Review
- Article
- Sterol regulation of developmental and oncogenic Hedgehog signaling.Biochemical pharmacology · 2022Review
- Pathways and Mechanisms of Cellular Cholesterol Efflux-Insight From Imaging.Frontiers in cell and developmental biology · 2022Review
- Measuring and Manipulating Membrane Cholesterol for the Study of Hedgehog Signaling.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Molecular basis of accessible plasma membrane cholesterol recognition by the GRAM domain of GRAMD1b.The EMBO journal · 2021Article
- Preparation and utility of asymmetric lipid vesicles for studies of perfringolysin O-lipid interactions.Methods in enzymology · 2021Article
- Cholesterol access in cellular membranes controls Hedgehog signaling.Nature chemical biology · 2020Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies have shown that cooperative interactions in endoplasmic reticulum (ER) membranes between Scap, cholesterol, and Insig result in switch-like control over activation of SREBP-2 transcription factors. This allows cells to rapidly adjust rates of cholesterol synthesis and uptake in response to even slight deviations from physiological set-point levels, thereby ensuring cholesterol homeostasis. In the present study we directly probe for the accessibility of cholesterol in purified ER membranes. Using a soluble cholesterol-binding bacterial toxin, perfringolysin O, we show that cholesterol accessibility increases abruptly at ∼5 mol % ER cholesterol, the same concentration at which SREBP-2 activation is halted. This switch-like change in cholesterol accessibility is observed not only in purified ER membranes but also in liposomes made from ER lipid extracts. The accessibility of cholesterol in membranes is related to its chemical activity. Complex formation between cholesterol and some ER phospholipids can result in sharp changes in cholesterol chemical activity and its accessibility to perfringolysin O or membrane sensors like Scap. The control of the availability of the cholesterol ligand to participate in cooperative Scap/cholesterol/Insig interactions further sharpens the sensitive switch that exerts precise control over cholesterol levels in cell membranes.
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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.