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Angiomotins link F-actin architecture to Hippo pathway signaling
The Hippo pathway regulates the transcriptional coactivator YAP to control cell proliferation, organ size, and stem cell maintenance. Multiple factors, such as substrate stiffness, cell density, and G protein–coupled receptor signaling, regulate YAP through their effects on the F-actin cytoskeleton,...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019498/ https://www.ncbi.nlm.nih.gov/pubmed/24648494 http://dx.doi.org/10.1091/mbc.E13-11-0701 |
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author | Mana-Capelli, Sebastian Paramasivam, Murugan Dutta, Shubham McCollum, Dannel |
author_facet | Mana-Capelli, Sebastian Paramasivam, Murugan Dutta, Shubham McCollum, Dannel |
author_sort | Mana-Capelli, Sebastian |
collection | PubMed |
description | The Hippo pathway regulates the transcriptional coactivator YAP to control cell proliferation, organ size, and stem cell maintenance. Multiple factors, such as substrate stiffness, cell density, and G protein–coupled receptor signaling, regulate YAP through their effects on the F-actin cytoskeleton, although the mechanism is not known. Here we show that angiomotin proteins (AMOT130, AMOTL1, and AMOTL2) connect F-actin architecture to YAP regulation. First, we show that angiomotins are required to relocalize YAP to the cytoplasm in response to various manipulations that perturb the actin cytoskeleton. Second, angiomotins associate with F-actin through a conserved F-actin–binding domain, and mutants defective for F-actin binding show enhanced ability to retain YAP in the cytoplasm. Third, F-actin and YAP compete for binding to AMOT130, explaining how F-actin inhibits AMOT130-mediated cytoplasmic retention of YAP. Furthermore, we find that LATS can synergize with F-actin perturbations by phosphorylating free AMOT130 to keep it from associating with F-actin. Together these results uncover a mechanism for how F-actin levels modulate YAP localization, allowing cells to make developmental and proliferative decisions based on diverse inputs that regulate actin architecture. |
format | Online Article Text |
id | pubmed-4019498 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-40194982014-07-30 Angiomotins link F-actin architecture to Hippo pathway signaling Mana-Capelli, Sebastian Paramasivam, Murugan Dutta, Shubham McCollum, Dannel Mol Biol Cell Articles The Hippo pathway regulates the transcriptional coactivator YAP to control cell proliferation, organ size, and stem cell maintenance. Multiple factors, such as substrate stiffness, cell density, and G protein–coupled receptor signaling, regulate YAP through their effects on the F-actin cytoskeleton, although the mechanism is not known. Here we show that angiomotin proteins (AMOT130, AMOTL1, and AMOTL2) connect F-actin architecture to YAP regulation. First, we show that angiomotins are required to relocalize YAP to the cytoplasm in response to various manipulations that perturb the actin cytoskeleton. Second, angiomotins associate with F-actin through a conserved F-actin–binding domain, and mutants defective for F-actin binding show enhanced ability to retain YAP in the cytoplasm. Third, F-actin and YAP compete for binding to AMOT130, explaining how F-actin inhibits AMOT130-mediated cytoplasmic retention of YAP. Furthermore, we find that LATS can synergize with F-actin perturbations by phosphorylating free AMOT130 to keep it from associating with F-actin. Together these results uncover a mechanism for how F-actin levels modulate YAP localization, allowing cells to make developmental and proliferative decisions based on diverse inputs that regulate actin architecture. The American Society for Cell Biology 2014-05-15 /pmc/articles/PMC4019498/ /pubmed/24648494 http://dx.doi.org/10.1091/mbc.E13-11-0701 Text en © 2014 Mana-Capelli et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Mana-Capelli, Sebastian Paramasivam, Murugan Dutta, Shubham McCollum, Dannel Angiomotins link F-actin architecture to Hippo pathway signaling |
title | Angiomotins link F-actin architecture to Hippo pathway signaling |
title_full | Angiomotins link F-actin architecture to Hippo pathway signaling |
title_fullStr | Angiomotins link F-actin architecture to Hippo pathway signaling |
title_full_unstemmed | Angiomotins link F-actin architecture to Hippo pathway signaling |
title_short | Angiomotins link F-actin architecture to Hippo pathway signaling |
title_sort | angiomotins link f-actin architecture to hippo pathway signaling |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019498/ https://www.ncbi.nlm.nih.gov/pubmed/24648494 http://dx.doi.org/10.1091/mbc.E13-11-0701 |
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