GSBS Student Publications
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology; Program in Cell Dynamics
Date
5-2014
Document Type
Article
Medical Subject Headings
Actin Cytoskeleton; Actins; Adaptor Proteins, Signal Transducing; Binding Sites; Carrier Proteins; Cell Line; HEK293 Cells; HeLa Cells; Humans; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Phosphoproteins; Phosphorylation; Protein Binding; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases; RNA Interference; RNA, Small Interfering; Signal Transduction; Tumor Suppressor Proteins
Disciplines
Amino Acids, Peptides, and Proteins | Biochemistry | Cell Biology | Cells | Molecular Biology
Abstract
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.
Rights and Permissions
Citation: Mol Biol Cell. 2014 May;25(10):1676-85. doi: 10.1091/mbc.E13-11-0701. Epub 2014 Mar 19. Link to article on publisher's site
DOI of Published Version
10.1091/mbc.E13-11-0701
Related Resources
Journal Title
Molecular biology of the cell
PubMed ID
24648494
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.
Repository Citation
Mana-Capelli, Sebastian; Paramasivam, Murugan; Dutta, Shubham; and McCollum, Dannel, "Angiomotins link F-actin architecture to Hippo pathway signaling" (2014). GSBS Student Publications. 1895.
https://escholarship.umassmed.edu/gsbs_sp/1895
Included in
Amino Acids, Peptides, and Proteins Commons, Biochemistry Commons, Cell Biology Commons, Cells Commons, Molecular Biology Commons
Comments
© 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).