dc.contributor.author | Sero, JE | |
dc.contributor.author | Bakal, C | |
dc.date.accessioned | 2017-01-27T14:55:35Z | |
dc.date.issued | 2017-01-25 | |
dc.identifier.citation | Cell systems, 2017, 4 (1), pp. 84 - 96.e6 | |
dc.identifier.issn | 2405-4712 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/394 | |
dc.identifier.eissn | 2405-4720 | |
dc.identifier.doi | 10.1016/j.cels.2016.11.015 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.format.extent | 84 - 96.e6 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Extracellular Matrix | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | cdc42 GTP-Binding Protein | |
dc.subject | rac1 GTP-Binding Protein | |
dc.subject | rhoA GTP-Binding Protein | |
dc.subject | Adaptor Proteins, Signal Transducing | |
dc.subject | GTPase-Activating Proteins | |
dc.subject | Cell Cycle Proteins | |
dc.subject | Nuclear Proteins | |
dc.subject | Transcription Factors | |
dc.subject | Cell Adhesion | |
dc.subject | Signal Transduction | |
dc.subject | Cell Movement | |
dc.subject | Cell Shape | |
dc.subject | Protein Processing, Post-Translational | |
dc.subject | Phosphorylation | |
dc.subject | Female | |
dc.subject | Single-Cell Analysis | |
dc.subject | Rho Guanine Nucleotide Exchange Factors | |
dc.title | Multiparametric Analysis of Cell Shape Demonstrates that β-PIX Directly Couples YAP Activation to Extracellular Matrix Adhesion. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-11-30 | |
rioxxterms.versionofrecord | 10.1016/j.cels.2016.11.015 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-01-05 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell systems | |
pubs.issue | 1 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Dynamical Cell Systems | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Dynamical Cell Systems | |
pubs.publication-status | Published | |
pubs.volume | 4 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Dynamical Cell Systems | |
dc.contributor.icrauthor | Bakal, Christopher | |