Multiparametric Analysis of Cell Shape Demonstrates that β-PIX Directly Couples YAP Activation to Extracellular Matrix Adhesion.
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Date
2017-01-25ICR Author
Author
Sero, JE
Bakal, C
Type
Journal Article
Metadata
Show full item recordAbstract
Mechanical signals from the extracellular matrix (ECM) and cellular geometry regulate the nuclear translocation of transcriptional regulators such as Yes-associated protein (YAP). Elucidating how physical signals control the activity of mechanosensitive proteins poses a technical challenge, because perturbations that affect cell shape may also affect protein localization indirectly. Here, we present an approach that mitigates confounding effects of cell-shape changes, allowing us to identify direct regulators of YAP localization. This method uses single-cell image analysis and statistical models that exploit the naturally occurring heterogeneity of cellular populations. Through systematic depletion of all human kinases, Rho family GTPases, GEFs, and GTPase activating proteins (GAPs), together with targeted chemical perturbations, we found that β-PIX, a Rac1/Ccd42 GEF, and PAK2, a Rac1/Cdc42 effector, drive both YAP activation and cell-ECM adhesion turnover during cell spreading. Our observations suggest that coupling YAP to adhesion dynamics acts as a mechano-timer, allowing cells to rapidly tune gene expression in response to physical signals.
Collections
Subject
Cell Line, Tumor
Extracellular Matrix
Humans
Breast Neoplasms
cdc42 GTP-Binding Protein
rac1 GTP-Binding Protein
rhoA GTP-Binding Protein
Adaptor Proteins, Signal Transducing
GTPase-Activating Proteins
Cell Cycle Proteins
Nuclear Proteins
Transcription Factors
Cell Adhesion
Signal Transduction
Cell Movement
Cell Shape
Protein Processing, Post-Translational
Phosphorylation
Female
Single-Cell Analysis
Rho Guanine Nucleotide Exchange Factors
Research team
Dynamical Cell Systems
Language
eng
Date accepted
2016-11-30
License start date
2017-01-05
Citation
Cell systems, 2017, 4 (1), pp. 84 - 96.e6
Publisher
CELL PRESS
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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