GSBS Student Publications

Student Author(s)

Shubham Dutta

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

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).

Related Resources

Link to Article in PubMed

Journal Title

Molecular biology of the cell

PubMed ID

24648494

Creative Commons License

Creative Commons Attribution-Noncommercial-Share Alike 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.