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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yoon, Joshua Weiss, Lucien E. Scott, Matthew P. Moerner, W. E. Su, Yourong S. Milenkovic, Ljiljana Roth, Theodore L. Sahl, Steffen J. |
| Description | Author Affiliation: Milenkovic L ( Department of Developmental Biology, Genetics and Bioengineering, Stanford University, Stanford, CA 94305); Weiss LE ( Department of Chemistry, Stanford University, Stanford, CA 94305); Yoon J ( Department of Chemistry, Stanford University, Stanford, CA 94305); Roth TL ( Department of Developmental Biology, Genetics and Bioengineering, Stanford University, Stanford, CA 94305); Su YS ( Department of Developmental Biology, Genetics and Bioengineering, Stanford University, Stanford, CA 94305); Sahl SJ ( Department of Chemistry, Stanford University, Stanford, CA 94305); Scott MP ( Department of Developmental Biology, Genetics and Bioengineering, Stanford University, Stanford, CA 94305); Moerner WE ( Department of Chemistry, Stanford University, Stanford, CA 94305); |
| Abstract | Accumulation of the signaling protein Smoothened (Smo) in the membrane of primary cilia is an essential step in Hedgehog (Hh) signal transduction, yet the molecular mechanisms of Smo movement and localization are poorly understood. Using ultrasensitive single-molecule tracking with high spatial/temporal precision (30 nm/10 ms), we discovered that binding events disrupt the primarily diffusive movement of Smo in cilia at an array of sites near the base. The affinity of Smo for these binding sites was modulated by the Hh pathway activation state. Activation, by either a ligand or genetic loss of the negatively acting Hh receptor Patched-1 (Ptch), reduced the affinity and frequency of Smo binding at the base. Our findings quantify activation-dependent changes in Smo dynamics in cilia and highlight a previously unknown step in Hh pathway activation. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 27 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Metabolism Hedgehog Proteins Receptors, Cell Surface Receptors, G-Protein-Coupled Algorithms Animals Cell Tracking Cells, Cultured Embryo, Mammalian Cytology Fibroblasts Genetics Kinetics Mice, Knockout Mice, Transgenic Microscopy, Confocal Protein Binding Signal Transduction Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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