Actin nucleators in the nucleus: an emerging theme

Abstract

SummaryActin is an integral component of the cytoskeleton, forming a plethora of macromolecular structures that mediate various cellular functions. The formation of such structures relies on the ability of actin monomers to associate into polymers, and this process is regulated by actin nucleation factors. These factors use monomeric actin pools at specific cellular locations, thereby permitting rapid actin filament formation when required. It has now been established that actin is also present in the nucleus, where it is implicated in chromatin remodelling and the regulation of eukaryotic gene transcription. Notably, the presence of typical actin filaments in the nucleus has not been demonstrated directly. However, studies in recent years have provided evidence for the nuclear localisation of actin nucleation factors that promote cytoplasmic actin polymerisation. Their localisation to the nucleus suggests that these proteins mediate collaboration between the cytoskeleton and the nucleus, which might be dependent on their ability to promote actin polymerisation. The nature of this cooperation remains enigmatic and it will be important to elucidate the physiological relevance of the link between cytoskeletal actin networks and nuclear events. This Commentary explores the current evidence for the nuclear roles of actin nucleation factors. Furthermore, the implication of actin-associated proteins in relaying exogenous signals to the nucleus, particularly in response to cellular stress, will be considered.

Morpho/Proteomic Comparative between High Grade Pleomorphic Sarcoma and Metastasis Diagnosed in an Old Captive Common Hippo

“…The G-actin isoform is converted into F-actin by nucleation and subsequently polymerizes and depolymerizes through a recycling process (treadmilling). [61][62][63] Decreased levels of β-actin can be a consequence of cytoskeletal organization changes causing reduction of organization during cell division and increased protrusions, cell motility and chromatin remodeling. 64,65 Significant levels of β-actin in metastatic tissue suggest a heterogeneous mechanism for formation of the primary tumor.…”

Insights into the effects of disease‐causing mutations in human actins

“…1). In the cytosol, the role of actin is built around the filament, whereas in the nucleus, function has been associated with both monomeric and filamentous actin [McDonald et al, 2006;Vartiainen et al, 2007; Fenn et al, 2011a,b;Weston et al, 2012;Zuchero et al, 2012;Belin et al, 2013;Kapoor et al, 2013].…”

“…Actin is an abundant 42 kD monomeric protein, found in virtually all eukaryotic cells, that can cycle between either a monomeric (G-actin) or polymeric (F-actin) state. It plays both contractile and structural roles in the cytoplasm, and recent studies have documented that actin in the nucleus acts as a promoter of transcription or as a member of a number of chromatin remodeling complexes Philimonenko et al, 2004;Miyamoto and Gurdon, 2011; Miyamoto et al, 2011a,b;Weston et al, 2012].G-actin is a clam-shaped protein with two domains, the inner and outer domains ( Fig. 1), connected by a hinge region, and separated by a deep cleft.…”

“…1). In the cytosol, the role of actin is built around the filament, whereas in the nucleus, function has been associated with both monomeric and filamentous actin [McDonald et al, 2006;Vartiainen et al, 2007; Fenn et al, 2011a,b;Weston et al, 2012;Zuchero et al, 2012;Belin et al, 2013;Kapoor et al, 2013].The actin filament is a conformationally dynamic structure whose behavior reflects the behavior of the actin monomer itself, and these multiple conformational states of actin are important for proper actin function [Schutt et al, 1993;Cedergren-Zeppezauer et al, 1994; Dominguez and There is a conformational-dependent maturation of the filament during polymerization [Carlier, 1990;Bryan and Rubenstein, 2005] which has been shown to be important for its interaction with different actin binding proteins. Such an example is caldesmon [Jensen et al, 2012], a protein involved in regulating filament stability in smooth muscle and non-muscle cells.…”

Functions of nuclear actin-binding proteins in human cancer (Review)

“…In the cytoplasm, actin is associated with numerous cellular activities, including sustaining cellular morphology, determining cellular organelle distribution, mediating intracellular transfer, endocytosis and exocytosis, cell division, cell migration and adhesion (4)(5)(6)(7)(8). Meanwhile, ABPs regulate actin cytoskeletal structure by modulating actin filament cross-linking into networks or depolymerizing into monomers, allowing actin to switch between the polymeric (F-actin form, filamentous actin) and monomeric state (G-actin form, globular actin) (2,9).…”