Actin on DNA—An ancient and dynamic relationship

Abstract

In the cytoplasm of eukaryotic cells the coordinated assembly of actin filaments drives essential cell biological processes, such as cell migration. The discovery of prokaryotic actin homologues, as well as the appreciation of the existence of nuclear actin, have expanded the scope by which the actin family is utilized in different cell types. In bacteria, actin has been implicated in DNA movement tasks, while the connection with the RNA polymerase machinery appears to exist in both prokaryotes and eukaryotes. Within the nucleus, actin has further been shown to play a role in chromatin remodeling and RNA processing, possibly acting to link these to transcription, thereby facilitating the gene expression process. The molecular mechanism by which actin exerts these newly discovered functions is still unclear, because while polymer formation seems to be required in bacteria, these species lack conventional actin-binding proteins to regulate the process. Furthermore, although the nucleus contains a plethora of actin-regulating factors, the polymerization status of actin within this compartment still remains unclear. General theme, however, seems to be actin's ability to interact with numerous binding partners. A common feature to the novel modes of actin utilization is the connection between actin and DNA, and here we aim to review the recent literature to explore how this connection is exploited in different contexts. V C 2010 Wiley-Liss, Inc.Key Words: actin, myosin, DNA, nucleus, transcription Introduction S ince the discovery of actin, a great number of actin-binding proteins (ABPs) have been found and implicated in various cellular processes. Traditionally, the reign of actin and ABPs has been limited to the cytoplasm, where they cooperate to form helical actin filaments, which can be bundled and cross-linked to different structural ends. The coordinated assembly of these filaments then drives for example cell migration, cytokinesis and membrane dynamics [reviewed in Pollard and Borisy, 2003]. However, during the past decade, actin has been transformed from an exclusively cytoskeletal component in eukaryotic cells to a multipurpose tool that most cells use in a number of processes. Especially the discovery of a function for actin in the nucleus [reviewed in Vartiainen, 2008] and identification of prokaryotic actin homologues [van den Ent et al., 2001] has yielded surprising data, which has considerably expanded the modes by which the actin family is utilized in different functional contexts. In the nucleus, actin has been shown to be involved all the way in the gene expression process from chromatin remodeling complexes through transcription to spliceosome function and mRNA export [reviewed in Percipalle, 2009]. In addition, nuclear actin also seems to affect the expression of subsets of genes by regulating the activity of specific transcription factors [Vartiainen et al., 2007]. However, the biochemical details of most of these actin-involving processes are lacking, and the nature and mechanics of the interact...

The actin nucleation factor JMY is a negative regulator of neuritogenesis

“…A second question concerns why JMY combines two very different cellular functions—transcriptional regulation and actin assembly—in one protein. Given the emerging role for nuclear actin in transcription regulation (Skarp and Vartiainen, 2010), it is tempting to speculate that JMY acts as a molecular link between the actin cytoskeleton and the transcription machinery. It will be important to examine transcription- and actin-related functions of JMY in cellular processes, including neuritogenesis, to understand whether they work together or independently.…”

The role of exportin 6 in cytoskeletal-mediated cell death and cell adhesion in human non-small-cell lung carcinoma cells following doxorubicin treatment

“…The mechanisms of the nucleocytoplasmic transport of actin tend to be very complex on account of the size of actin and because of the lack of a classical nuclear localization signal (NLS) [14]. It has also been suggested that many actin-binding proteins have NLS, which thus makes it possible to import actin into the nucleus [15].…”

Nuclear F-actin Formation and Reorganization upon Cell Spreading

“…Thus, modulation of nuclear actin likely depends and is critically influenced by the signaling context as well as shuttling dynamics of its regulating factors. It is therefore not surprising that the formation of nuclear F-actin has been controversially discussed up to the point that nuclear actin was considered to be entirely or mainly monomeric in its nature (5)(6)(7)(8)(9). Recently, we and others have demonstrated the existence of nuclear F-actin structures in somatic cell nuclei using actin probes, which are specifically targeted to the nucleus (10,11).…”