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Actin is not only one of the most abundant proteins in eukaryotic cells, but also one of the most versatile. In addition to its familiar involvement in enabling contraction and establishing cellular motility and scaffolding in the cytosol, actin has well-documented roles in a variety of processes within the confines of the nucleus, such as transcriptional regulation and DNA repair. Interestingly, monomeric actin as well as actin-related proteins (Arps) are found as stoichiometric subunits of a variety of chromatin remodeling complexes and histone acetyltransferases, raising the question of precisely what roles they serve in these contexts. Actin and Arps are present in unique combinations in chromatin modifiers, helping to establish structural integrity of the complex and enabling a wide range of functions, such as recruiting the complex to nucleosomes to facilitate chromatin remodeling and promoting ATPase activity of the catalytic subunit. Actin and Arps are also thought to help modulate chromatin dynamics and maintain higher-order chromatin structure. Moreover, the presence of actin and Arps in several chromatin modifiers is necessary for promoting genomic integrity and an effective DNA damage response. In this review, we discuss the involvement of actin and Arps in these nuclear complexes that control chromatin remodeling and histone modifications, while also considering avenues for future study to further shed light on their functional importance.

Actin is not only one of the most abundant proteins in eukaryotic cells, but also one of the most versatile. In addition to its familiar involvement in enabling contraction and establishing cellular motility and scaffolding in the cytosol, actin has well-documented roles in a variety of processes within the confines of the nucleus, such as transcriptional regulation and DNA repair. Interestingly, monomeric actin as well as actin-related proteins (Arps) are found as stoichiometric subunits of a variety of chromatin remodeling complexes and histone acetyltransferases, raising the question of precisely what roles they serve in these contexts. Actin and Arps are present in unique combinations in chromatin modifiers, helping to establish structural integrity of the complex and enabling a wide range of functions, such as recruiting the complex to nucleosomes to facilitate chromatin remodeling and promoting ATPase activity of the catalytic subunit. Actin and Arps are also thought to help modulate chromatin dynamics and maintain higher-order chromatin structure. Moreover, the presence of actin and Arps in several chromatin modifiers is necessary for promoting genomic integrity and an effective DNA damage response. In this review, we discuss the involvement of actin and Arps in these nuclear complexes that control chromatin remodeling and histone modifications, while also considering avenues for future study to further shed light on their functional importance. [ABSTRACT FROM AUTHOR]

Nuclear actin family proteins, comprising of actin and actin-related proteins (Arps), are essential functional components of the multiple chromatin remodeling complexes. The INO80 chromatin remodeling complex, which is evolutionarily conserved and has roles in transcription, DNA replication and repair, consists of actin and actin-related proteins Arp4, Arp5, and Arp8. We generated Arp5 knockout (KO) and Arp8 KO cells from the human Nalm-6 pre-B cell line and used these KO cells to examine the roles of Arp5 and Arp8 in the transcriptional regulation mediated by the INO80 complex. In both of Arp5 KO and Arp8 KO cells, the oxidative stress-induced expression of HMOX1 gene, encoding for heme oxygenase-1 (HO-1), was significantly impaired. Consistent with these observations, chromatin immunoprecipitation (ChIP) assay revealed that oxidative stress caused an increase in the binding of the INO80 complex to the regulatory sites of HMOX1 in wild-type cells. The binding of INO80 complex to chromatin was reduced in Arp8 KO cells compared to that in the wild-type cells. On the other hand, the binding of INO80 complex to chromatin in Arp5 KO cells was similar to that in the wild-type cells even under the oxidative stress condition. However, both remodeling of chromatin at the HMOX1 regulatory sites and binding of a transcriptional activator to these sites were impaired in Arp5 KO cells, indicating that Arp5 is required for the activation of the INO80 complex. Collectively, these results suggested that these nuclear Arps play indispensable roles in the function of the INO80 chromatin remodeling complex. [ABSTRACT FROM AUTHOR]

Whilst it is recognized that contraction plays an important part in maintaining the structure and function of mature skeletal muscle, its role during development remains undefined. In this study the role of movement in skeletal muscle maturation was investigated in intact zebrafish embryos using a combination of genetic and pharmacological approaches. An immotile mutant line (cacnb1ts25) which lacks functional voltage-gated calcium channels (dihydropyridine receptors) in the muscle and pharmacological immobilization of embryos with a reversible anesthetic (Tricaine), allowed the study of paralysis (in mutants and anesthetized fish) and recovery of movement (reversal of anesthetic treatment). The effect of paralysis in early embryos (aged between 17 and 24 hours post-fertilization, hpf) on skeletal muscle structure at both myofibrillar and myofilament level was determined using both immunostaining with confocal microscopy and small angle X-ray diffraction. The consequences of paralysis and subsequent recovery on the localization of the actin capping proteins Tropomodulin 1 & 4 (Tmod) in fish aged from 17 hpf until 42 hpf was also assessed. The functional consequences of early paralysis were investigated by examining the mechanical properties of the larval muscle. The length-force relationship, active and passive tension, was measured in immotile, recovered and control skeletal muscle at 5 and 7 day post-fertilization (dpf). Recovery of muscle function was also assessed by examining swimming patterns in recovered and control fish. Inhibition of the initial embryonic movements (up to 24 hpf) resulted in an increase in myofibril length and a decrease in width followed by almost complete recovery in both moving and paralyzed fish by 42 hpf. In conclusion, myofibril organization is regulated by a dual mechanism involving movement-dependent and movement-independent processes. The initial contractile event itself drives the localization of Tmod1 to its sarcomeric position, capping the actin pointed ends and ultimately regulating actin length. This study demonstrates that both contraction and contractile-independent mechanisms are important for the regulation of myofibril organization, which in turn is necessary for establishing proper skeletal muscle structure and function during development in vivo in zebrafish. [ABSTRACT FROM AUTHOR]

In plant cells the actin cytoskeleton adopts many configurations, but is best understood as an unstable, interconnected track that rearranges to define the patterns of long distance transport of organelles during growth. Actin filaments do not form spontaneously; instead filament nucleators, such as the evolutionarily conserved actin-related protein (ARP) 2/3 complex, can efficiently generate new actin filament networks when in a fully activated state. A growing number of genetic experiments have shown that ARP2/3 is necessary for morphogenesis in processes that range from tip growth during root nodule formation to the diffuse polarized growth of leaf trichomes and pavement cells. Although progress has been rapid in the identification of proteins that function in series to positively regulate ARP2/3, less has been learned about the actual function of ARP2/3 in cells. In this paper, we analyze the localization of ARP2/3 in Arabidopsis leaf pavement cells. We detect a pool of ARP2/3 in the nucleus, and also find that ARP2/3 is efficiently and specifically clustered on multiple organelle surfaces and associates with both the actin filament and microtubule cytoskeletons. Our mutant analyses and ARP2/3 and actin double labeling experiments indicate that the clustering of ARP2/3 on organelle surfaces and an association with actin bundles does not necessarily reflect an active pool of ARP2/3, and instead most of the complex appears to exist as a latent organelle-associated pool. [ABSTRACT FROM AUTHOR]

In the human experience SCARs are permanent reminders of past events, not always based on bad decisions, but always those in which an interplay of opposing forces leaves behind a clear record in the form of some permanent watery mark. During plant morphogenesis, SCARs are important proteins that reflect an unusual evolutionary outcome, in which the plant kingdom relies heavily on this single class of actin-related protein (ARP) 2/3 complex activator to dictate the time and place of actin filament nucleation. This unusually simple arrangement may serve as a permanent reminder that cell shape control in plants is fundamentally different from that of crawling cells in mammals that use the power of actin polymerization to define and maintain cell shape. In plant cells, actin filaments indirectly affect cell shape by determining the transport properties of organelles and cargo molecules that modulate the mechanical properties of the wall. It is becoming increasingly clear that polarized bundles of actin filaments operate at whole cell spatial scales to organize the cytoplasm and dictate the patterns of long-distance intracellular transport and secretion. The number of actin-binding proteins and actin filament nucleators that are known to participate in the process of actin network formation are rapidly increasing. In plants, formins and ARP2/3 are two important actin filament nucleators. This review will focus on ARP2/3, and the apparent reliance of most plant species on the SCAR/WAVE regulatory complex as the sole pathway for ARP2/3 activation. [ABSTRACT FROM AUTHOR]