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Differential regulation of the Hippo pathway by adherens junctions and apical-basal cell polarity modules

Yang, Chih-Chao, Graves, Hillary K., Moya, Ivan M., Tao, Chunyao, Hamaratoglu Dion, Fisun, Gladden, Andrew B. and Halder, Georg 2015. Differential regulation of the Hippo pathway by adherens junctions and apical-basal cell polarity modules. Proceedings of the National Academy of Sciences 112 (6) , pp. 1785-1790. 10.1073/pnas.1420850112

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Abstract

Adherens junctions (AJs) and cell polarity complexes are key players in the establishment and maintenance of apical–basal cell polarity. Loss of AJs or basolateral polarity components promotes tumor formation and metastasis. Recent studies in vertebrate models show that loss of AJs or loss of the basolateral component Scribble (Scrib) cause deregulation of the Hippo tumor suppressor pathway and hyperactivation of its downstream effectors Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ). However, whether AJs and Scrib act through the same or independent mechanisms to regulate Hippo pathway activity is not known. Here, we dissect how disruption of AJs or loss of basolateral components affect the activity of the Drosophila YAP homolog Yorkie (Yki) during imaginal disc development. Surprisingly, disruption of AJs and loss of basolateral proteins produced very different effects on Yki activity. Yki activity was cell-autonomously decreased but non–cell-autonomously elevated in tissues where the AJ components E-cadherin (E-cad) or α-catenin (α-cat) were knocked down. In contrast, scrib knockdown caused a predominantly cell-autonomous activation of Yki. Moreover, disruption of AJs or basolateral proteins had different effects on cell polarity and tissue size. Simultaneous knockdown of α-cat and scrib induced both cell-autonomous and non–cell-autonomous Yki activity. In mammalian cells, knockdown of E-cad or α-cat caused nuclear accumulation and activation of YAP without overt effects on Scrib localization and vice versa. Therefore, our results indicate the existence of multiple, genetically separable inputs from AJs and cell polarity complexes into Yki/YAP regulation

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: National Academy of Sciences
ISSN: 0027-8424
Date of Acceptance: 1 January 2015
Last Modified: 08 Feb 2019 15:45
URI: http://orca.cf.ac.uk/id/eprint/118485

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