PUBLICATION
Optogenetic control of YAP cellular localisation and function
- Authors
- Toh, P.J.Y., Lai, J.K.H., Hermann, A., Destaing, O., Sheetz, M.P., Sudol, M., Saunders, T.E.
- ID
- ZDB-PUB-220726-29
- Date
- 2022
- Source
- EMBO reports 23(9): e54401 (Journal)
- Registered Authors
- Lai, Jason, Saunders, Timothy Edward
- Keywords
- YAP, cell proliferation, optogenetics, spatiotemporal dynamics, zebrafish
- MeSH Terms
-
- Animals
- Cell Nucleus/metabolism
- Cell Proliferation/physiology
- Optogenetics
- Signal Transduction*
- Zebrafish*/genetics
- PubMed
- 35876586 Full text @ EMBO Rep.
Citation
Toh, P.J.Y., Lai, J.K.H., Hermann, A., Destaing, O., Sheetz, M.P., Sudol, M., Saunders, T.E. (2022) Optogenetic control of YAP cellular localisation and function. EMBO reports. 23(9):e54401.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping