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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,...

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Autores principales: Mana-Capelli, Sebastian, Paramasivam, Murugan, Dutta, Shubham, McCollum, Dannel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
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.
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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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AT duttashubham angiomotinslinkfactinarchitecturetohippopathwaysignaling
AT mccollumdannel angiomotinslinkfactinarchitecturetohippopathwaysignaling