Tracking down the different forms of nuclear actin (original) (raw)

Nuclear actin dynamics – From form to function

FEBS Letters, 2008

Cell biological functions of actin have recently expanded from cytoplasm to nucleus, with actin implicated in such diverse processes as gene expression, transcription factor regulation and intranuclear motility. Actin in the nucleus seems to behave differently than in the cytoplasm, raising new questions regarding the molecular mechanisms by which actin functions in cells. In this review, I will discuss dynamic properties of nuclear actin that are related to its polymerization cycle and nucleocytoplasmic shuttling. By comparing the behaviour of nuclear and cytoplasmic actin and their regulators, I try to dissect the underlying differences of these equally important cellular actin pools.

Structural biochemistry of nuclear actin-related proteins 4 and 8 reveals their interaction with actin

Embo Journal, 2011

Nuclear actin and actin related proteins (Arps) are integral components of various chromatin remodeling complexes. Actin in such nuclear assemblies does not form filaments but associates in defined complexes, for instance with Arp4 and Arp8 in the INO80 remodeler. To understand the relationship between nuclear actin and its associated Arps and to test the possibility that Arp4 and Arp8 help maintain actin in defined states, we structurally analyzed Arp4 and Arp8 from Saccharomyces cerevisiae and tested their biochemical effects on actin assembly and disassembly. The solution structures of isolated Arp4 and Arp8 indicate them to be monomeric and the crystal structure of ATP-Arp4 reveals several intriguing differences to actin that explain why Arp4 does not form filaments itself. Remarkably, Arp4, assisted by Arp8, influences actin polymerization in vitro and is able to depolymerize actin filaments by complex formation with monomeric ADP-actin via the barbed end. Our data suggest a likely assembly between actin and Arp4, explaining how nuclear actin is held in a discrete complex within the INO80 chromatin remodeler.

Actin isoforms in the cell nucleus

Actin, a major component of the cytoplasm, is also abundant in the nucleus. Nuclear actin is involved in a variety of nuclear processes that include transcription, chromatin remodeling and intranuclear transport. While the involvement of actin in these processes has been established, it is not quite clear how the functions of actin in the nucleus are regulated. We now show that nuclear, but not cytoplasmic actin is modified by SUMO proteins, specifically by SUMO2 and SUMO3. By using a combinatorial approach of computational modeling and site directed mutagenesis, we identified the lysines at position K68 and K284 as critical sites for SUMOylation of actin and present a model of the SUMO-actin complex. We also demonstrate that SUMOylation of actin is important for the retention of actin in the nucleus. We show that mutations in actin that prevent SUMOylation lead to a rapid export of actin from the nucleus through an Exportin 1 dependent pathway that can be inhibited by Leptomycin B. In conclusion, we demonstrate the first nuclear posttranslational modification of actin and show that this modification indeed regulates some of the nuclear functions of actin.

Actin: From structural plasticity to functional diversity

European Journal of Cell Biology, 2011

This article addresses the multiple activities of actin. Starting out with the history of actin's discovery, purification and structure, it emphasizes the close relation between structure and function. In this context, we also point to unconventional actin conformations. Their existence in living cells is not yet well documented, however, they seem to play a special role in the supramolecular patterning that underlies some of the physiological functions of actin. Conceivably, such conformations may contribute to actin's diverse activities in the nucleus that are poorly understood so far.

Nucleoplasmic -actin exists in a dynamic equilibrium between low-mobility polymeric species and rapidly diffusing populations

The Journal of Cell Biology, 2006

541-552 http://www.jcb.org/cgi/doi/10.1083/jcb. 200507101 JCB 541 < d o i > 1 0 . 1 0 8 3 / j c b . 2 0 0 5 0 7 1 0 1 < / d o i > < a i d > 2 0 0 5 0 7 1 0 1 < / a i d > Nucleoplasmic β-actin exists in a dynamic equilibrium between low-mobility polymeric species and rapidly diffusing populations β -Actin, once thought to be an exclusively cytoplasmic protein, is now known to have important functions within the nucleus. Nuclear β-actin associates with and functions in chromatin remodeling complexes, ribonucleic acid polymerase complexes, and at least some ribonucleoproteins. Proteins involved in regulating actin polymerization are also found in the interphase nucleus. We defi ne the dynamic properties of nuclear actin molecules using fl uorescence recovery after photobleaching.

Actin: From cell biology to atomic detail

Biology of the Cell, 1999

Over the past 2 decades our knowledge about actin filaments has evolved from a rigid ''pearls on a string'' model to that of a complex, highly dynamic protein polymer which can now be analyzed at atomic detail. To achieve this, exploring actin's oligomerization, polymerization, polymorphism, and dynamic behavior has been crucial to understanding in detail how this abundant and ubiquitous protein can fulfill its various functions within living cells. In this review, a correlative view of a number of distinct aspects of actin is presented, and the functional implications of recent structural, biochemical, and mechanical data are critically evaluated. Rational analysis of these various experimental data is achieved using an integrated structural approach which combines intermediate-resolution electron microscopy-based 3-D reconstructions of entire actin filaments with atomic resolution X-ray data of monomeric and polymeric actin. r 1997 Academic Press

Conformation-specific antibodies reveal distinct actin structures in the nucleus and the cytoplasm

Journal of Structural Biology, 2005

For many years the existence of actin in the nucleus has been doubted because of the lack of phalloidin staining as well as the failure to document nuclear actin filaments by electron microscopy. More recent findings reveal actin to be a component of chromatin remodeling complexes and of the machinery involved in RNA synthesis and transport. With distinct functions for

Nuclear actin and protein 4.1: Essential interactions during nuclear assembly in vitro

Proceedings of the National Academy of Sciences, 2003

Structural protein 4.1, which has crucial interactions within the spectrin–actin lattice of the human red cell membrane skeleton, also is widely distributed at diverse intracellular sites in nucleated cells. We previously showed that 4.1 is essential for assembly of functional nuclei in vitro and that the capacity of 4.1 to bind actin is required. Here we report that 4.1 and actin colocalize in mammalian cell nuclei using fluorescence microscopy and, by higher-resolution detergent-extracted cell whole-mount electron microscopy, are associated on nuclear filaments. We also devised a cell-free assay using Xenopus egg extract containing fluorescent actin to follow actin during nuclear assembly. By directly imaging actin under nonperturbing conditions, the total nuclear actin population is retained and visualized in situ relative to intact chromatin. We detected actin initially when chromatin and nuclear pores began assembling. As nuclear lamina assembled, but preceding DNA synthesis, a...

Actin complexes in the cell nucleus: new stones in an old field

Histochemistry and Cell Biology, 2010

Actin is a well-known protein that has shown a myriad of activities in the cytoplasm. However, recent findings of actin involvement in nuclear processes are overwhelming. Actin complexes in the nucleus range from very dynamic chromatin-remodeling complexes to structural elements of the matrix with single partners known as actin-binding proteins (ABPs). This review summarizes the recent findings of actin-containing complexes in the nucleus. Particular attention is given to key processes like chromatin remodeling, transcription, DNA replication, nucleocytoplasmic transport and to actin roles in nuclear architecture. Understanding the mechanisms involving ABPs will definitely lead us to the principles of the regulation of gene expression performed via concerting nuclear and cytoplasmic processes.