TY - JOUR T1 - Active maintenance of nuclear actin by importin 9 supports transcription. JF - Proc Natl Acad Sci U S A Y1 - 2012 A1 - Dopie, Joseph A1 - Skarp, Kari-Pekka A1 - Rajakylä, Eeva Kaisa A1 - Tanhuanpää, Kimmo A1 - Vartiainen, Maria K KW - Actin Depolymerizing Factors KW - Actins KW - Active Transport, Cell Nucleus KW - Animals KW - beta Karyopherins KW - Cell Line KW - Cytoplasm KW - drosophila melanogaster KW - Drosophila Proteins KW - Genes, Reporter KW - Genetic Complementation Test KW - Green Fluorescent Proteins KW - Humans KW - Karyopherins KW - Mice KW - Microscopy, Confocal KW - NIH 3T3 Cells KW - Photobleaching KW - ran GTP-Binding Protein KW - Receptors, Cytoplasmic and Nuclear KW - Recombinant Fusion Proteins KW - RNA Interference KW - RNA, Small Interfering KW - Transcription, Genetic AB -

Besides its essential and well established role as a component of the cytoskeleton, actin is also present in the cell nucleus, where it has been linked to many processes that control gene expression. For example, nuclear actin regulates the activity of specific transcription factors, associates with all three RNA polymerases, and is a component of many chromatin remodelling complexes. Despite the fact that two export receptors, Crm1 and exportin 6, have been linked to nuclear export of actin, the mechanism by which actin enters the nucleus to elicit these essential functions has not been determined. It is also unclear whether actin is actively exchanged between the nucleus and the cytoplasm, and whether this connection has any functional significance for the cell. By applying a variety of live-cell imaging techniques we revealed that actin constantly shuttles in and out of the nucleus. The fast transport rates, which depend on the availability of actin monomers, suggest an active transport mechanism in both directions. Importantly, we identified importin 9 as the nuclear import factor for actin. Furthermore, our RNAi experiments showed that the active maintenance of nuclear actin levels by importin 9 is required for maximal transcriptional activity. Measurements of nuclear export rates and depletion studies also clarified that nuclear export of actin is mediated by exportin 6, and not by Crm1. These results demonstrate that cytoplasmic and nuclear actin pools are dynamically connected and identify the nuclear import and export mechanisms of actin.

VL - 109 IS - 9 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22323606?dopt=Abstract ER -