ArticleProceedings of the National Academy of Sciences of the United States of America2019
Motional dynamics of single Patched1 molecules in cilia are controlled by Hedgehog and cholesterol.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
- 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
- BMP4 regulates asymmetric Pkd2 distribution in mouse nodal immotile cilia and ciliary mechanosensing required for left-right determination.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Drug and siRNA screens identify ROCK2 as a therapeutic target for ciliopathies.Communications medicine · 2025Article
- Collaborative role of two distinct cilium-specific cytoskeletal systems in driving Hedgehog-responsive transcription factor trafficking.Science advances · 2025Article
- Loss of Sc5d results in micrognathia due to a failure in osteoblast differentiation.Journal of advanced research · 2024Article
- IFT cargo and motors associate sequentially with IFT trains to enter cilia of C. elegans.Nature communications · 2024Article
- A Pilot Immunohistochemical Study Identifies Hedgehog Pathway Expression in Sinonasal Adenocarcinoma.International journal of molecular sciences · 2024Article
- Transport and barrier mechanisms that regulate ciliary compartmentalization and ciliopathies.Nature reviews. Nephrology · 2024Review
- Structure, function, and research progress of primary cilia in reproductive physiology and reproductive diseases.Frontiers in cell and developmental biology · 2024Review
- 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
- The Energetics and Ion Coupling of Cholesterol Transport Through Patched1.bioRxiv : the preprint server for biology · 2023Article
- Single-molecule imaging in the primary cilium.Methods in cell biology · 2023Article
- Characterizing locus specific chromatin structure and dynamics with correlative conventional and super-resolution imaging in living cells.Nucleic acids research · 2022Article
- A local interplay between diffusion and intraflagellar transport distributes TRPV-channel OCR-2 along C. elegans chemosensory cilia.Communications biology · 2022Article
- CNPY4 inhibits the Hedgehog pathway by modulating membrane sterol lipids.Nature communications · 2022Article
- Structural basis for catalyzed assembly of the Sonic hedgehog-Patched1 signaling complex.Developmental cell · 2022Article
- Sterol regulation of developmental and oncogenic Hedgehog signaling.Biochemical pharmacology · 2022Review
- Direct imaging of intraflagellar-transport turnarounds reveals that motors detach, diffuse, and reattach to opposite-direction trains.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Relative Affinities of Protein-Cholesterol Interactions from Equilibrium Molecular Dynamics Simulations.Journal of chemical theory and computation · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The Hedgehog-signaling pathway is an important target in cancer research and regenerative medicine; yet, on the cellular level, many steps are still poorly understood. Extensive studies of the bulk behavior of the key proteins in the pathway established that during signal transduction they dynamically localize in primary cilia, antenna-like solitary organelles present on most cells. The secreted Hedgehog ligand Sonic Hedgehog (SHH) binds to its receptor Patched1 (PTCH1) in primary cilia, causing its inactivation and delocalization from cilia. At the same time, the transmembrane protein Smoothened (SMO) is released of its inhibition by PTCH1 and accumulates in cilia. We used advanced, single molecule-based microscopy to investigate these processes in live cells. As previously observed for SMO, PTCH1 molecules in cilia predominantly move by diffusion and less frequently by directional transport, and spend a fraction of time confined. After treatment with SHH we observed two major changes in the motional dynamics of PTCH1 in cilia. First, PTCH1 molecules spend more time as confined, and less time freely diffusing. This result could be mimicked by a depletion of cholesterol from cells. Second, after treatment with SHH, but not after cholesterol depletion, the molecules that remain in the diffusive state showed a significant increase in the diffusion coefficient. Therefore, PTCH1 inactivation by SHH changes the diffusive motion of PTCH1, possibly by modifying the membrane microenvironment in which PTCH1 resides.
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