< Terug naar vorige pagina
Cells lacking U+03B2-actin are genetically reprogrammed and maintain conditional migratory capacity
Tijdschriftbijdrage - Tijdschriftartikel
Ondertitel:Cells lacking beta-actin are genetically reprogrammed and maintain conditional migratory capacity
Vertebrate nonmuscle cells express two actin isoforms: cytoplasmic beta- and gamma-actin. Because of the presence and localized translation of beta-actin at the leading edge, this isoform is generally accepted to specifically generate protrusive forces for cell migration. Recent evidence also implicates beta-actin in gene regulation. Cell migration without beta-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 beta-actin display compensatory expression of other actin isoforms. Consistent with this preservation of polymerization capacity, beta-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 beta-actin knockout cells. This also explains why reintroducing beta-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 beta- actin knockout cells based on increased Rho-ROCK signaling and increased TGF beta production resulting in increased adhesion and contractility in the knockout cells. Inhibiting ROCK or myosin restores migration of beta- actin knockout cells indicating that other actins compensate for beta- actin in this process. Consequently, isoactins act redundantly in providing propulsive forces for cell migration, but beta-actin has a unique nuclear function, regulating expression on transcriptional and post-translational levels, thereby preventing myogenic differentiation.
Tijdschrift: MOLECULAR & CELLULAR PROTEOMICS
Pagina's: 255 - 271
Jaar van publicatie:2012