ArticleeLife2016
Cholesterol activates the G-protein coupled receptor Smoothened to promote Hedgehog signaling.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
163 citing papers in PubMed, 241 citations in OpenAlex.
- The orientation of cholesterol's hydroxy group affects its membrane dynamics and intracellular transport.iScience · 2026Article
- Primary cilia: master conductors of cellular communication in development and disease.Nature reviews. Nephrology · 2026Review
- Receptor allostery promotes context-specific Sonic Hedgehog signaling during embryonic development.Nature communications · 2026Article
- Structural mechanism for noncanonical GPCR signaling in the Hedgehog pathway.Nature structural & molecular biology · 2026Article
- Article
- A cell-based Sonic Hedgehog signaling transduction system to identify additive and synergistic chemical interactions.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Starve-Feed Cycles Direct Quiescence to Proliferation Transitions inbioRxiv : the preprint server for biology · 2026Article
- Lipid ciliology: specialized ciliary membrane lipids in physiology and disease.Frontiers in cell and developmental biology · 2026Review
- Lipid metabolic reprogramming in clear cell renal cell carcinoma: focus on high-density lipoprotein-related pathways.Oncology reviews · 2026Review
- Oncogenic B-Raf proto-oncogene, serine/threonine kinase-mediated hedgehog signalling in the pathogenesis and targeted therapy of melanoma.World journal of clinical oncology · 2025Review
- Lipid metabolism in cancer stem cells: reprogramming, mechanisms, crosstalk, and therapeutic approaches.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- 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
- Cholesterol allosteric modulation of the oxytocin receptor.Biophysical journal · 2025Article
- Molecular architecture of human LYCHOS involved in lysosomal cholesterol signaling.Nature structural & molecular biology · 2025Article
- Dysregulation of cholesterol homeostasis in cancer pathogenesis.Cellular and molecular life sciences : CMLS · 2025Review
- Direct effect of membrane environment on the activation of mGluR2 revealed by single-molecule FRET.Structure (London, England : 1993) · 2025Article
- Embryotoxicity of statins and other prescribed drugs with reported off-target effects on cholesterol biosynthesis.Reproductive toxicology (Elmsford, N.Y.) · 2025Article
- 7-Dehydrocholesterol Reductase Activates the Hedgehog Pathway by Regulating Cholesterol to Promote the Development of Triple-Negative Breast Cancer.Current cancer drug targets · 2025Article
- Review
- A bitter anti-inflammatory drug binds at two distinct sites of a human bitter taste GPCR.Nature communications · 2024Article
103 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol is not just necessary but also sufficient to activate signaling by the Hedgehog (Hh) pathway, a prominent cell-cell communication system in development. Cholesterol influences Hh signaling by directly activating Smoothened (SMO), an orphan GPCR that transmits the Hh signal across the membrane in all animals. Unlike many GPCRs, which are regulated by cholesterol through their heptahelical transmembrane domains, SMO is activated by cholesterol through its extracellular cysteine-rich domain (CRD). Residues shown to mediate cholesterol binding to the CRD in a recent structural analysis also dictate SMO activation, both in response to cholesterol and to native Hh ligands. Our results show that cholesterol can initiate signaling from the cell surface by engaging the extracellular domain of a GPCR and suggest that SMO activity may be regulated by local changes in cholesterol abundance or accessibility.
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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.