Nuclear actin modulates cell motility via transcriptional regulation of adhesive and cytoskeletal genes

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http://hdl.handle.net/10138/167941

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Sharili , A S , Kenny , F N , Vartiainen , M K & Connelly , J T 2016 , ' Nuclear actin modulates cell motility via transcriptional regulation of adhesive and cytoskeletal genes ' , Scientific Reports , vol. 6 , 33893 . https://doi.org/10.1038/srep33893

Julkaisun nimi: Nuclear actin modulates cell motility via transcriptional regulation of adhesive and cytoskeletal genes
Tekijä: Sharili, Amir S.; Kenny, Fiona N.; Vartiainen, Maria K.; Connelly, John T.
Muu tekijä: University of Helsinki, Institute of Biotechnology
Päiväys: 2016-09-21
Kieli: eng
Sivumäärä: 9
Kuuluu julkaisusarjaan: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/167941
Tiivistelmä: 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 beta-actin or beta-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.
Avainsanat: SERUM RESPONSE FACTOR
DYNAMICS
SRF
OOCYTES
ANTIBODIES
COMPLEXES
BINDING
1182 Biochemistry, cell and molecular biology
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