Cells lacking ß-actin are genetically reprogrammed and maintain conditional migratory capacity.
Mol Cell Proteomics
; 11(8): 255-71, 2012 Aug.
Article
em En
| MEDLINE
| ID: mdl-22448045
ABSTRACT
Vertebrate nonmuscle cells express two actin isoforms cytoplasmic ß- and γ-actin. Because of the presence and localized translation of ß-actin at the leading edge, this isoform is generally accepted to specifically generate protrusive forces for cell migration. Recent evidence also implicates ß-actin in gene regulation. Cell migration without ß-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 ß-actin display compensatory expression of other actin isoforms. Consistent with this preservation of polymerization capacity, ß-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 ß-actin knockout cells. This also explains why reintroducing ß-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 ß-actin knockout cells based on increased Rho-ROCK signaling and increased TGFß production resulting in increased adhesion and contractility in the knockout cells. Inhibiting ROCK or myosin restores migration of ß-actin knockout cells indicating that other actins compensate for ß-actin in this process. Consequently, isoactins act redundantly in providing propulsive forces for cell migration, but ß-actin has a unique nuclear function, regulating expression on transcriptional and post-translational levels, thereby preventing myogenic differentiation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
/
Actinas
/
Proteômica
/
Fibroblastos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Mol Cell Proteomics
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Bélgica