Document Detail

Cells lacking β-actin are genetically reprogrammed and maintain conditional migratory capacity.
MedLine Citation:
PMID:  22448045     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article     Date:  2012-03-22
Journal Detail:
Title:  Molecular & cellular proteomics : MCP     Volume:  11     ISSN:  1535-9484     ISO Abbreviation:  Mol. Cell Proteomics     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-08     Completed Date:  2012-12-21     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  101125647     Medline TA:  Mol Cell Proteomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  255-71     Citation Subset:  IM    
Department of Medical Protein Research, VIB, Ghent, Belgium.
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MeSH Terms
Actins / genetics,  metabolism*
Amides / pharmacology
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, 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
Reg. No./Substance:
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 Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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