title: Nuclear actin modulates cell motility via transcriptional regulation of adhesive and cytoskeletal genes.
abstract: The actin cytoskeleton is a classic biomechanical mediator of cell migration. While it is known that actin also shuttles in and out of the nucleus, its functions within this compartment remain poorly understood. In this study, we investigated how nuclear actin regulates keratinocyte gene expression and cell behavior. Gene expression profiling of normal HaCaT keratinocytes compared to HaCaTs over-expressing wild-type β-actin or β-actin tagged with a nuclear localization sequence (NLS-actin), identified multiple adhesive and cytoskeletal genes, such as MYL9, ITGB1, and VCL, which were significantly down-regulated in keratinocytes with high levels of nuclear actin. In addition, genes associated with transcriptional regulation and apoptosis were up-regulated in cells over expressing NLS-actin. Functionally, accumulation of actin in the nucleus altered cytoskeletal and focal adhesion organization and inhibited cell motility. Exclusion of endogenous actin from the nucleus by knocking down Importin 9 reversed this phenotype and enhanced cell migration. Based on these findings, we conclude that the level of actin in the nucleus is a transcriptional regulator for tuning keratinocyte migration.
authors.affiliation: Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, U.K.
authors.forename: Amir S
authors.initials: AS
authors.lastname: Sharili
authors.affiliation: Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, U.K.
authors.forename: Fiona N
authors.initials: FN
authors.lastname: Kenny
authors.affiliation: Institute of Biotechnology, University of Helsinki, 00790 Helsinki, Finland.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Vartiainen
authors.affiliation: Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, U.K.|Institute of Bioengineering, Queen Mary University of London, London E1 2AT, U.K.
authors.forename: John T
authors.initials: JT
authors.lastname: Connelly
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D009687:Nuclear Proteins