Abstract
Circumferential actin belts underlying the adherens junctions of columnar epithelial cell monolayers control intercellular surface tension and cell shape to maintain tissue integrity. Yes-associated protein (YAP) and its paralog TAZ are proliferation-activating transcriptional coactivators that shuttle between the nucleus and cytoplasm. Previous studies suggest the importance of stress fibers in the actin cytoskeleton for regulation of YAP nuclear localization; however, the role of the circumferential actin belt on YAP localization remains unclarified. By manipulating actin tension, we demonstrate that circumferential actin belt tension suppresses YAP/TAZ nuclear localization. This suppression requires Merlin, an F-actin binding protein associated with adherens junctions. Merlin physically interacts with YAP/TAZ, and nuclear export sequences of Merlin are required for suppression. Together, with the observation that the association between E-cadherin and Merlin was diminished by tension in circumferential actin belts, our results suggest that released Merlin undergoes nucleocytoplasmic shutting and mediates export of YAP/TAZ from the nucleus.
| Original language | English |
|---|---|
| Pages (from-to) | 1435-1447 |
| Number of pages | 13 |
| Journal | Cell Reports |
| Volume | 20 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2017 Aug 8 |
| Externally published | Yes |
Keywords
- Hippo
- Merlin
- TAZ
- YAP
- circumferential actin belt
- epithelial cell
- mechanotransduction
- nuclear export
- proliferation
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)