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

Posted on Posted in AMRC Research

Date: 16 Aug 2017

 

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.

 

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Shigeo OHNO

E-mail: ohnos@med.yokohama-cu.ac.jp   Phone: +81 45 352 8871

Special Contract Professor, Department of Molecular Biology
Yokohama City University, Graduate School of Medicine
Fukuura 3-9, Kanazawa-ku Yokohama, Japan 236-0004