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Optogenetic control of YAP cellular localisation and function
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Toh, Pearlyn J. Y., Lai, Jason K. H., Hermann, Anke, Destaing, Olivier, Sheetz, Michael P., Sudol, Marius and Saunders, Timothy E. (2022) Optogenetic control of YAP cellular localisation and function. EMBO reports . e54401. doi:10.15252/embr.202154401
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Official URL: https://doi.org/10.15252/embr.202154401
Abstract
YAP, an effector of the Hippo signalling pathway, promotes organ growth and regeneration. Prolonged YAP activation results in uncontrolled proliferation and cancer. Therefore, exogenous regulation of YAP activity has potential translational applications. We present a versatile optogenetic construct (optoYAP) for manipulating YAP localisation, and consequently its activity and function. We attach a LOV2 domain that photocages a nuclear localisation signal (NLS) to the N‐terminus of YAP. In 488 nm light, the LOV2 domain unfolds, exposing the NLS, which shuttles optoYAP into the nucleus. Nuclear import of optoYAP is reversible and tuneable by light intensity. In cell culture, activated optoYAP promotes YAP target gene expression and cell proliferation. Similarly, optofYap can be used in zebrafish embryos to modulate target genes. We demonstrate that optoYAP can override a cell's response to substrate stiffness to generate anchorage‐independent growth. OptoYAP is functional in both cell culture and in vivo, providing a powerful tool to address basic research questions and therapeutic applications in regeneration and disease.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QL Zoology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | |||||||||
| SWORD Depositor: | Library Publications Router | |||||||||
| Library of Congress Subject Headings (LCSH): | Optogenetics, Cell proliferation, Logperch | |||||||||
| Journal or Publication Title: | EMBO reports | |||||||||
| Publisher: | Nature Publishing Group | |||||||||
| ISSN: | 1469-221X | |||||||||
| Official Date: | 25 July 2022 | |||||||||
| Dates: |
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| Page Range: | e54401 | |||||||||
| DOI: | 10.15252/embr.202154401 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Reuse Statement (publisher, data, author rights): | ** Licence for VoR version of this article: http://creativecommons.org/licenses/by/4.0/ | |||||||||
| Access rights to Published version: | Open Access | |||||||||
| Copyright Holders: | © 2022 The Authors. Published under the terms of the CC BY 4.0 license | |||||||||
| RIOXX Funder/Project Grant: |
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