The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Selective translocation of intracellular Smoothened to the primary cilium in response to Hedgehog pathway modulation
Open accessAbstract
Smoothened (Smo), a 7-pass transmembrane protein, is essential for transduction of a Hedgehog (Hh) signal across the cell membrane. Smo is also the principle therapeutic target for several candidate drugs in the treatment of Hh-related diseases. Mammalian Smo translocates to the primary cilium in response to Sonic hedgehog (Shh) ligand-mediated signaling. A mechanistic understanding of Smo translocation and its interactions with drug candidates is pivotal to our understanding of Hh signaling and the design, development and application of successful drugs. We established a system in which Smo was dual-labeled with GFP and a 12-aa tag whose recognition by an enzymatic process enables the posttranslational labeling of Smo in the cell membrane within the living cell. These tools enable the simultaneous visualization of all cellular Smo, and more specifically, the cell membrane restricted subpopulation. Using this system, we demonstrate that cyclopamine, a widely used Hh antagonist, induces a cilial translocation of Smo similar to that reported for Shh ligand and several Hh agonists. In contrast, other antagonists abrogate the Shh-induced, cilial translocation of Smo. We present evidence that the majority of cilial-localized Smo originates from an intracellular source and may traffic to the primary cilium through an intraflagellar transport (IFT) pathway.
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Cites
Vertebrate Smoothened functions at the primary cilium
Corbit, K. C., Aanstad, P., Singla, V., Norman, A. R., Stainier, D. Y. R., & Reiter, J. F. (2005) · Nature · doi:10.1038/nature04117 · Cited by 1,481
Patched1 Regulates Hedgehog Signaling at the Primary Cilium
Rohatgi, R., Milenkovic, L., & Scott, M. P. (2007) · Science · doi:10.1126/science.1139740 · Cited by 1,426
Nachury, M. V., Loktev, A. V., Zhang, Q., Westlake, C. J., Peränen, J., Merdes, A., Slusarski, D. C., Scheller, R. H., Bazan, J. F., Sheffield, V. C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.03.053 · Cited by 1,384
Haycraft, C. J., Banizs, B., Aydin-Son, Y., Zhang, Q., Michaud, E. J., & Yoder, B. K. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010053 · Cited by 902
Cilia and Hedgehog responsiveness in the mouse
Huangfu, D., & Anderson, K. V. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505328102 · Cited by 820
Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells
Han, Y.-G., Spassky, N., Romaguera-Ros, M., Garcia-Verdugo, J.-M., Aguilar, A., Schneider-Maunoury, S., & Alvarez-Buylla, A. (2008) · Nature Neuroscience · doi:10.1038/nn2059 · Cited by 547
Svärd, J., Henricson, K. H., Persson-Lek, M., Rozell, B., Lauth, M., Bergström, Å., Ericson, J., Toftgård, R., & Teglund, S. (2006) · Developmental Cell · doi:10.1016/j.devcel.2005.12.013 · Cited by 468
Cited by
The mechanisms of Hedgehog signalling and its roles in development and disease
Briscoe, J., & Thérond, P. P. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3598 · Cited by 1,751
Catenacci, D. V. T., Junttila, M. R., Karrison, T., Bahary, N., Horiba, M. N., Nattam, S. R., Marsh, R., Wallace, J., Kozloff, M., Rajdev, L., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.62.8719 · Cited by 561
Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth
Kim, J., Tang, J. Y., Gong, R., Kim, J., Lee, J. J., Clemons, K. V., Chong, C. R., Chang, K. S., Fereshteh, M., Gardner, D., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.02.027 · Cited by 527
The Hedgehog Signal Transduction Network
Robbins, D. J., Fei, D. L., & Riobo, N. A. (2012) · Science Signaling · doi:10.1126/scisignal.2002906 · Cited by 419
The Hedgehog's tale: developing strategies for targeting cancer
Ng, J. M. Y., & Curran, T. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3079 · Cited by 398
Metadata
- Authors
- Wang, Y., Zhou, Z., Walsh, C. T., & McMahon, A. P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-02-24
- Volume
- 106
- Issue
- 8
- Pages
- 2623-2628
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2023040415
- Cited by
- 199
- References
- 7
- FWCI
- 10.08
- Type
- journal article
- Language
- en
- Open access
- green
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- Wang, Y., Zhou, Z., Walsh, C. T., & McMahon, A. P. (2009). Selective translocation of intracellular Smoothened to the primary cilium in response to Hedgehog pathway modulation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0812110106
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
