Actin was first isolated from the muscle cells, in which this protein is one of the main components of the actomyosin motor [1]. Subsequently, it turned out that actin is present in every cell of the body. At the end of the twentieth century, modern ideas about the role of actin in the formation of the cytoskeleton, cell motility, interaction of cells with the environment, and cell division were formed [2–5]. The process of actin polymerization - depolymerization was studied in detail, the main actin-bound proteins were identified that are involved in the initiation of the polymerization of actin monomers, elongation and branching of F-actin, the formation of the cytoskeleton in the cytoplasm of cells and contractile fibers in muscle cells [6].
Almost simultaneously with actin in the cytoplasm of non-muscle cells, actin was found in the cell nucleus [7–11]. However, the existence of nuclear actin has long caused great skepticism among researchers [12]. This was mainly due to the fact that actin filaments (F-actin) could not be detected in the nucleus. In addition, the abundance of actin in the cytoplasm did not exclude the possibility that the actin detected in the nucleus or nuclear fractions was an admixture of the cytoplasmic actin. Finally, the absence of F-actin in the nucleus has called into question the functional significance of nuclear actin. All this slowed down the development of nuclear actin research for several decades. However, achievements over the past 15 years have convincingly demonstrated not only the existence of nuclear actin, but also its significant functional role in various nuclear processes [13, 14].
In recent years, thanks to the development of new technologies, a detailed study of nuclear actin has become possible, and many studies have appeared devoted to the study of its functional role. In particular, it was shown that although actin does not have a nuclear localization signal, monomeric G-actin constantly moves between the nucleus and the cytoplasm. It has been shown that actin moves from the cytoplasm to the nucleus through nuclear pores in a complex with caffeline and importin 9, and from the nucleus into the cytoplasm in a complex with profilin and exportin 6 [15, 16]. It has been shown that most nuclear actin exists in monomeric form, with dimers and oligomers also observed [17–20]. If in the cytoplasm, actin monomers are considered as simple building blocks of F-actin filaments, then in the nucleus the functional role of G-actin is much more diverse. Nuclear G-actin is a subunit of several chromatin remodeling and modifying complexes that control chromatin structure and accessibility by regulating nucleosome repositioning and histone modifications [21, 22]. It has been shown that there are two components of chromatin mobility: Brownian motion and actin / ATP-dependent motion, which allows reordering of chromatin compaction that is important during transcription or repair [23, 24].
Nuclear actin regulates various transcription factors and interacts with all RNA polymerases [25–28]. Since changes in chromatin and genome architecture are known attributes of embryonic and postembryonic cell differentiation and correlate with various diseases, an important role of nuclear actin is that it participates in the differentiation programs during neurogenesis, myogenesis, organ formation, and the development of various diseases [29, 30]. The multifunctionality of nuclear actin suggests that nuclear actin is also important for immune cell differentiation and function [31–33]. In addition, nuclear actin is involved in apoptosis [34], counteracting viral infection [35], changing the structure of the nuclear membrane [36–39], and DNA repair [40].
Therefore, if in the cytoplasm actin is mainly present in the F-form and plays a structural-motor role, then in the cell nucleus, most of the actin is present in the G-form and interacts with nuclear proteins, chromatin, and DNA. Furthermore, in the nucleus, there are polymeric forms of actin that differ from F-actin [41–43], called “short oligomers” of nuclear actin or “rods” [44]. It is known that under normal conditions, these structures are dynamic, but under stress and disease they are persistent and their number increases [33, 44, 45]. We assume that “short oligomers” of nuclear actin may be similar to the so-called inactivated actin, a monodisperse associate consisting of 14–16 monomers that appears in vitro under any denaturing influences [46–48]. We also assume that the formation of inactivated actin is associated with a specific pathway of oligomerization of actin monomers in vitro and that this situation may be associated with the differences in actin-binding proteins in the cytoplasm and in the cell nucleus.
Cells are crowded with macromolecules and all proteins are permanently in contact with their neighbor. This became especially evident with the discovery of intrinsically disordered proteins (IDPs). IDPs are always in interaction with other proteins or nucleic acids. The actin interactome is significantly wider than that of other globular proteins [49]. Actin, which has more than 800 proteins in its interactome, is more similar to an IDP hub than to a globular protein [50]. Well-studied actin-binding proteins are only a small part of the proteins interacting with cytoplasmic and nuclear actin. In this regard, we decided to conduct a bioinformatics analysis of the actin interactome and compare the interactomes of cytoplasmic and nuclear actin.