title: Steady-state nuclear actin levels are determined by export competent actin pool.
abstract: A number of studies in the last decade have irrevocably promoted actin into a fully fledged member of the nuclear compartment, where it, among other crucial tasks, facilitates transcription and chromatin remodeling. Changes in nuclear actin levels have been linked to different cellular processes: decreased nuclear actin to quiescence and increased nuclear actin to differentiation. Importin 9 and exportin 6 transport factors are responsible for the continuous nucleocytoplasmic shuttling of actin, but the mechanisms, which result in modulated actin levels, have not been characterized. We find that in cells growing under normal growth conditions, the levels of nuclear actin vary considerably from cell to cell. To understand the basis for this, we have extensively quantified several cellular parameters while at the same time recording the import and export rates of green fluorescent protein (GFP)-tagged actin. Surprisingly, our dataset shows that the ratio of nuclear to cytoplasmic fluorescence intensity, but not nuclear shape, size, cytoplasm size, or their ratio, correlates negatively with both import and export rate of actin. This suggests that high-nuclear actin content is maintained by both diminished import and export. The high nuclear actin containing cells still show high mobility of actin, but it is not export competent, suggesting increased binding of actin to nuclear complexes. Creation of such export incompetent actin pool would ensure enough actin is retained in the nucleus and make it available for the various nuclear functions described for actin.
authors.affiliation: Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki, Viikinkaari 9, 00014, Helsinki, Finland.
authors.forename: Kari-Pekka
authors.initials: KP
authors.lastname: Skarp
authors.forename: Guillaume
authors.initials: G
authors.lastname: Huet
authors.forename: Maria K
authors.initials: MK
authors.lastname: Vartiainen
mesh_terms: D000199:Actins / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D053144:Cell Nucleus Shape; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005453:Fluorescence; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D021381:Protein Transport
chemical_list: D000199:Actins; D049452:Green Fluorescent Proteins
keywords: actin; actin polymerization; nuclear transport; nucleo-cytoplasmic shuttling; nucleus