The Epithelial Circumferential Actin Belt Regulates YAP/TAZ through Nucleocytoplasmic Shuttling of Merlin

Publication date: 8 August 2017
Source:Cell Reports, Volume 20, Issue 6
Author(s): Kana T. Furukawa, Kazunari Yamashita, Natsuki Sakurai, Shigeo Ohno
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.

Graphical abstract

Teaser

Furukawa et al. demonstrate an actin cytoskeleton-mediated YAP/TAZ-regulatory mechanism by which circumferential actin belt contraction suppresses nuclear localization of YAP/TAZ. They further show that YAP/TAZ physically interacts with Merlin, and YAP/TAZ nucleocytoplasmic translocation is dependent on Merlin nuclear export sequences.


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