| Cells lacking β-actin are genetically reprogrammed and maintain conditional migratory capacity. | |
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MedLine Citation:
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PMID: 22448045 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Vertebrate nonmuscle cells express two actin isoforms: cytoplasmic β- and γ-actin. Because of the presence and localized translation of β-actin at the leading edge, this isoform is generally accepted to specifically generate protrusive forces for cell migration. Recent evidence also implicates β-actin in gene regulation. Cell migration without β-actin has remained unstudied until recently and it is unclear whether other actin isoforms can compensate for this cytoplasmic function and/or for its nuclear role. Primary mouse embryonic fibroblasts lacking β-actin display compensatory expression of other actin isoforms. Consistent with this preservation of polymerization capacity, β-actin knockout cells have unchanged lamellipodial protrusion rates despite a severe migration defect. To solve this paradox we applied quantitative proteomics revealing a broad genetic reprogramming of β-actin knockout cells. This also explains why reintroducing β-actin in knockout cells does not restore the affected cell migration. Pathway analysis suggested increased Rho-ROCK signaling, consistent with observed phenotypic changes. We therefore developed and tested a model explaining the phenotypes in β-actin knockout cells based on increased Rho-ROCK signaling and increased TGFβ production resulting in increased adhesion and contractility in the knockout cells. Inhibiting ROCK or myosin restores migration of β-actin knockout cells indicating that other actins compensate for β-actin in this process. Consequently, isoactins act redundantly in providing propulsive forces for cell migration, but β-actin has a unique nuclear function, regulating expression on transcriptional and post-translational levels, thereby preventing myogenic differentiation. |
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Authors:
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Davina Tondeleir; Anja Lambrechts; Matthias Müller; Veronique Jonckheere; Thierry Doll; Drieke Vandamme; Karima Bakkali; Davy Waterschoot; Marianne Lemaistre; Olivier Debeir; Christine Decaestecker; Boris Hinz; An Staes; Evy Timmerman; Niklaas Colaert; Kris Gevaert; Joël Vandekerckhove; Christophe Ampe |
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Publication Detail:
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Type: Journal Article Date: 2012-03-22 |
Journal Detail:
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Title: Molecular & cellular proteomics : MCP Volume: 11 ISSN: 1535-9484 ISO Abbreviation: Mol. Cell Proteomics Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-08-08 Completed Date: 2012-12-21 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 101125647 Medline TA: Mol Cell Proteomics Country: United States |
Other Details:
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Languages: eng Pagination: 255-71 Citation Subset: IM |
Affiliation:
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Department of Medical Protein Research, VIB, Ghent, Belgium. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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genetics,
metabolism* Amides / pharmacology Animals Blotting, Western Cell Adhesion / drug effects, genetics, physiology Cell Movement / drug effects, genetics, physiology* Cells, Cultured Embryo, Mammalian / cytology, embryology, metabolism Fibroblasts / cytology, metabolism* Gene Expression Regulation, Developmental Mice Mice, Knockout Protein Isoforms / genetics, metabolism Proteomics / methods* Pseudopodia / genetics, metabolism, physiology Pyridines / pharmacology Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / drug effects, genetics, physiology Transforming Growth Factor beta / genetics, metabolism rho-Associated Kinases / antagonists & inhibitors, genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Amides; 0/Protein Isoforms; 0/Pyridines; 0/Rock1 protein, mouse; 0/Rock2 protein, mouse; 0/Transforming Growth Factor beta; 138381-45-0/Y 27632; EC 2.7.11.1/rho-Associated Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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