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Role of α-Catenin and its mechanosensing properties in regulating Hippo/YAP-dependent tissue growth
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863567/ https://www.ncbi.nlm.nih.gov/pubmed/31697683 http://dx.doi.org/10.1371/journal.pgen.1008454 |
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author | Sarpal, Ritu Yan, Victoria Kazakova, Lidia Sheppard, Luka Yu, Jessica C. Fernandez-Gonzalez, Rodrigo Tepass, Ulrich |
author_facet | Sarpal, Ritu Yan, Victoria Kazakova, Lidia Sheppard, Luka Yu, Jessica C. Fernandez-Gonzalez, Rodrigo Tepass, Ulrich |
author_sort | Sarpal, Ritu |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6863567 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-68635672019-12-06 Role of α-Catenin and its mechanosensing properties in regulating Hippo/YAP-dependent tissue growth Sarpal, Ritu Yan, Victoria Kazakova, Lidia Sheppard, Luka Yu, Jessica C. Fernandez-Gonzalez, Rodrigo Tepass, Ulrich PLoS Genet Research Article 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. Public Library of Science 2019-11-07 /pmc/articles/PMC6863567/ /pubmed/31697683 http://dx.doi.org/10.1371/journal.pgen.1008454 Text en © 2019 Sarpal et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Sarpal, Ritu Yan, Victoria Kazakova, Lidia Sheppard, Luka Yu, Jessica C. Fernandez-Gonzalez, Rodrigo Tepass, Ulrich Role of α-Catenin and its mechanosensing properties in regulating Hippo/YAP-dependent tissue growth |
title | Role of α-Catenin and its mechanosensing properties in regulating Hippo/YAP-dependent tissue growth |
title_full | Role of α-Catenin and its mechanosensing properties in regulating Hippo/YAP-dependent tissue growth |
title_fullStr | Role of α-Catenin and its mechanosensing properties in regulating Hippo/YAP-dependent tissue growth |
title_full_unstemmed | Role of α-Catenin and its mechanosensing properties in regulating Hippo/YAP-dependent tissue growth |
title_short | Role of α-Catenin and its mechanosensing properties in regulating Hippo/YAP-dependent tissue growth |
title_sort | role of α-catenin and its mechanosensing properties in regulating hippo/yap-dependent tissue growth |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863567/ https://www.ncbi.nlm.nih.gov/pubmed/31697683 http://dx.doi.org/10.1371/journal.pgen.1008454 |
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