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PLoS Genet ; 15(11): e1008454, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31697683

RESUMO

α-catenin is a key protein of adherens junctions (AJs) with mechanosensory properties. It also acts as a tumor suppressor that limits tissue growth. Here we analyzed the function of Drosophila α-Catenin (α-Cat) in growth regulation of the wing epithelium. We found that different α-Cat levels led to a differential activation of Hippo/Yorkie or JNK signaling causing tissue overgrowth or degeneration, respectively. α-Cat can modulate Yorkie-dependent tissue growth through recruitment of Ajuba, a negative regulator of Hippo signaling to AJs but also through a mechanism independent of Ajuba recruitment to AJs. Both mechanosensory regions of α-Cat, the M region and the actin-binding domain (ABD), contribute to growth regulation. Whereas M is dispensable for α-Cat function in the wing, individual M domains (M1, M2, M3) have opposing effects on growth regulation. In particular, M1 limits Ajuba recruitment. Loss of M1 causes Ajuba hyper-recruitment to AJs, promoting tissue-tension independent overgrowth. Although M1 binds Vinculin, Vinculin is not responsible for this effect. Moreover, disruption of mechanosensing of the α-Cat ABD affects tissue growth, with enhanced actin interactions stabilizing junctions and leading to tissue overgrowth. Together, our findings indicate that α-Cat acts through multiple mechanisms to control tissue growth, including regulation of AJ stability, mechanosensitive Ajuba recruitment, and dynamic direct F-actin interactions.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Proteínas com Domínio LIM/genética , Asas de Animais/crescimento & desenvolvimento , alfa Catenina/genética , Citoesqueleto de Actina/genética , Actinas/genética , Junções Aderentes/genética , Animais , Morte Celular/genética , Citoesqueleto/genética , Drosophila melanogaster/crescimento & desenvolvimento , Epitélio/crescimento & desenvolvimento , Epitélio/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Sistema de Sinalização das MAP Quinases/genética , Mecanotransdução Celular/genética , Proteínas Nucleares/genética , Domínios Proteicos/genética , Proteínas Serina-Treonina Quinases/genética , Transativadores/genética , Vinculina/genética , Asas de Animais/metabolismo , Proteínas de Sinalização YAP
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