ArticleScience advances2022
Patched 1 regulates Smoothened by controlling sterol binding to its extracellular cysteine-rich domain.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Ciliary Membrane Lipid Homeostasis in Health and Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Receptor allostery promotes context-specific Sonic Hedgehog signaling during embryonic development.Nature communications · 2026Article
- Primary cilia-extracellular vesicle crosstalk in Alzheimer's disease: Emerging mechanisms and biomarker potential.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Research progress on the Sonic Hedgehog signaling pathway in the central nervous system: Novel insights.Neural regeneration research · 2026Article
- Pathophysiological significance of cholesterol in ciliopathies.Fujita medical journal · 2026Article
- Article
- TRV130 inhibits colon cancer progression via suppressing the Hedgehog signaling pathway: in vitro and in vivo evidence.Hereditas · 2026Article
- Cholesterol in hematological malignancies: metabolism, mechanisms, and clinical implications.Frontiers in immunology · 2026Review
- RhoE downregulation leads to enhanced cholesterol biosynthesis and sorafenib resistance in hepatocellular carcinoma.The Journal of biological chemistry · 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
- Multifaceted roles of sonic hedgehog signaling in mammalian inner ear development.Developmental biology · 2025Review
- Cholesterol allosteric modulation of the oxytocin receptor.Biophysical journal · 2025Article
- Regulatory mechanisms governing GLI proteins in hedgehog signaling.Anatomical science international · 2025Review
- Cortisol regulates neonatal lung development via Smoothened.Respiratory research · 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
- Loss of Sc5d results in micrognathia due to a failure in osteoblast differentiation.Journal of advanced research · 2024Article
- Two-way Dispatched function in Sonic hedgehog shedding and transfer to high-density lipoproteins.eLife · 2024Article
- Near-infrared imaging for visualizing the synergistic relationship between autophagy and NFS1 protein during multidrug resistance using an ICT-TICT integrated platform.Chemical science · 2024Article
- Decrypting orphan GPCR drug discovery via multitask learning.Journal of cheminformatics · 2024Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Smoothened (SMO) transduces the Hedgehog (Hh) signal across the plasma membrane in response to accessible cholesterol. Cholesterol binds SMO at two sites: one in the extracellular cysteine-rich domain (CRD) and a second in the transmembrane domain (TMD). How these two sterol-binding sites mediate SMO activation in response to the ligand Sonic Hedgehog (SHH) remains unknown. We find that mutations in the CRD (but not the TMD) reduce the fold increase in SMO activity triggered by SHH. SHH also promotes the photocrosslinking of a sterol analog to the CRD in intact cells. In contrast, sterol binding to the TMD site boosts SMO activity regardless of SHH exposure. Mutational and computational analyses show that these sites are in allosteric communication despite being 45 angstroms apart. Hence, sterols function as both SHH-regulated orthosteric ligands at the CRD and allosteric ligands at the TMD to regulate SMO activity and Hh signaling.
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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.