Details

Autor(en) / Beteiligte

• Yang, Chih-Chao
• Graves, Hillary K.
• Moya, Ivan M.
• Tao, Chunyao
• Hamaratoglu, Fisun
• Gladden, Andrew B.
• Halder, Georg

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2015-02, Vol.112 (6), p.1785-1790

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2015

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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 theDrosophilaYAP 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 componentsE-cadherin(E-cad) orα-catenin(α-cat) were knocked down. In contrast,scribknockdown 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 ofα-catandscribinduced both cell-autonomous and non–cell-autonomous Yki activity. In mammalian cells, knockdown ofE-cadorα-catcaused 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.