ArticleDevelopmental cell2022
Structural basis for catalyzed assembly of the Sonic hedgehog-Patched1 signaling complex.
Article in Developmental cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Research progress on the Sonic Hedgehog signaling pathway in the central nervous system: Novel insights.Neural regeneration research · 2026Article
- The Role of Hedgehog Signaling in Non-small Cell Lung Cancer: Targeting Tumor Invasion, Therapy Resistance and Novel Therapeutic Strategies.International journal of biological sciences · 2026Review
- Gas1 regulates embryonic tongue muscle proliferation, differentiation and maturation via alternative pathways to Hedgehog signaling.Development (Cambridge, England) · 2025Article
- IGSF10 is a RET antagonist regulating Ewing sarcoma growth and GnRH neuron migration.Cell reports · 2025Article
- Hedgehog-dependent and hedgehog-independent roles for growth arrest specific 1 in mammalian kidney morphogenesis.Development (Cambridge, England) · 2024Article
- Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers.Nature communications · 2024Article
- Extracellular carriers control lipid-dependent secretion, delivery, and activity of WNT morphogens.Developmental cell · 2024Article
- Cellular and molecular mechanisms of Hedgehog signalling.Nature reviews. Molecular cell biology · 2023Review
- The energetics and ion coupling of cholesterol transport through Patched1.Science advances · 2023Article
- Genomic alterations of oligodendrogliomas at distant recurrence.Cancer medicine · 2023Article
- The Inseparable Relationship Between Cholesterol and Hedgehog Signaling.Annual review of biochemistry · 2023Review
- The biology of SCUBE.Journal of biomedical science · 2023Review
- The Energetics and Ion Coupling of Cholesterol Transport Through Patched1.bioRxiv : the preprint server for biology · 2023Article
- Review
- Detection of various fusion genes by one-step RT-PCR and the association with clinicopathological features in 242 cases of soft tissue tumor.Frontiers in cell and developmental biology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The dually lipidated Sonic hedgehog (SHH) morphogen signals through the tumor suppressor membrane protein Patched1 (PTCH1) to activate the Hedgehog pathway, which is fundamental in development and cancer. SHH engagement with PTCH1 requires the GAS1 coreceptor, but the mechanism is unknown. We demonstrate a unique role for GAS1, catalyzing SHH-PTCH1 complex assembly in vertebrate cells by direct SHH transfer from the extracellular SCUBE2 carrier to PTCH1. Structure of the GAS1-SHH-PTCH1 transition state identifies how GAS1 recognizes the SHH palmitate and cholesterol modifications in modular fashion and how it facilitates lipid-dependent SHH handoff to PTCH1. Structure-guided experiments elucidate SHH movement from SCUBE2 to PTCH1, explain disease mutations, and demonstrate that SHH-induced PTCH1 dimerization causes its internalization from the cell surface. These results define how the signaling-competent SHH-PTCH1 complex assembles, the key step triggering the Hedgehog pathway, and provide a paradigm for understanding morphogen reception and its regulation.
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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.