Hippo signaling in Drosophila and mammals is prominent in regulating cell proliferation, death and differentiation. Hippo signaling effectors (YAP/TAZ) exhibit crosstalk with transforming growth factor-β (TGF-β)-Smad and Wnt-β-catenin pathways. Previously, we implicated Smad7 and β-catenin in myogenesis. Therefore, we assessed a potential role of TAZ on theSmad7/β-catenin complex in muscle cells. Here, we document functional interactions between Smad7, TAZ and β-catenin in myogenic cells. Ectopic TAZ expression resulted in repression of the muscle-specific creatine kinase muscle (ckm) gene promoter and its corresponding protein level. Depletion of endogenous TAZ enhanced ckm promoter activation. Ectopic TAZ, while potently active on a TEAD reporter (HIP-HOP), repressed myogenin and myod enhancer regions and Myogenin protein level. Additionally, a Wnt/β-catenin readout (TOP flash) demonstrated TAZ inhibition of β-catenin activity. In myoblasts, TAZ is predominantly localized in nuclear speckles, while in differentiation conditions TAZ is hyperphosphorylated at Ser 89 leading to enhanced cytoplasmic sequestration. Finally, live cell imaging indicates that TAZ exhibits properties of liquid-liquid phase separation (LLPS). These observations indicate that TAZ, as an effector of Hippo signaling, supresses the myogenic differentiation machinery.
TAZ exhibits phase separation properties and interacts with Smad7 and β-catenin to repress skeletal myogenesis
These authors contributed equally to the manuscript.
- Award Group:
- Funder(s): the Canadian Institute of Health Research
- Award Id(s): PJT-159644
- Funder(s):
Currently Viewing Accepted Manuscript - Newer Version Available
- Split-screen
- Views Icon Views
- Open the PDF for in another window
-
Article Versions Icon
Versions
- Version of Record 12 January 2022
- Accepted Manuscript 03 December 2021
- Share Icon Share
-
Tools Icon
Tools
- Search Site
Soma Tripathi, Tetsuaki Miyake, Jonathan Kelebeev, John C. McDermott; TAZ exhibits phase separation properties and interacts with Smad7 and β-catenin to repress skeletal myogenesis. J Cell Sci 2021; jcs.259097. doi: https://doi.org/10.1242/jcs.259097
Download citation file:
Advertisement
Imaging Cell Architecture and Dynamics
We are still welcoming submissions for our upcoming Special Issue: Imaging Cell Architecture and Dynamics. This issue will be coordinated by two Guest Editors: Lucy Collinson (The Francis Crick Institute, UK) and Guillaume Jacquemet (University of Turku, Finland). Extended submission deadline: 29 March 2024.
Journal of Cell Science - more than just a journal
People who know JCS well will know that we're more than just a journal and that our community – the cell biology community – really is at the heart of everything we do. Read the full Editorial by Editor-in-Chief Michael Way and Executive Editor Seema Grewal.
2024 Journal Meeting 'Diversity and Evolution in Cell Biology'
Registration is open for our 2024 Journal Meeting Diversity and Evolution in Cell Biology, which aims to bring together evolutionary biologists and cell biologists investigating diverse aspects of cellular physiology. Submit your abstract by 5 April. Final registration deadline: 3 May 2024.
Workshop: Roles of Lipids in Nuclear Homeostasis and Genome Stability
Early-career researchers interested in the roles of nuclear lipids, apply now for one of the ten funded places at this Workshop, which will take place 14-17 October 2024. Application deadline: 19 April.
Reasons to submit to Journal of Cell Science
There are many benefits to publishing in Journal of Cell Science - read more about why you should choose JCS or visit our submission page now.