2012/03/24 by Davina Tondeleir, Anja Lambrechts, Matthias Müller +15 · 2 citations
Biochemistry, Genetics and Molecular Biology · #Cellular Mechanics and Interactions #Viral Infectious Diseases and Gene Expression in Insects #Muscle Physiology and Disorders #Cell biology #Actin #Biology #Actin remodeling #Myosin #Cell migration #Profilin #Conditional gene knockout #Actin remodeling of neurons #Gene knockout #Actin cytoskeleton #Phenotype #Cell #Cytoskeleton #Genetics #Gene
paper · pdf · doi:10.1074/mcp.m111.015099
openalex publication_date 2012/03/24 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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.