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Journal of Biomechanics Jan 2010Dynamic regulation of the filamentous actin (F-actin) cytoskeleton is critical to numerous physical cellular processes, including cell adhesion, migration and division.... (Review)
Review
Dynamic regulation of the filamentous actin (F-actin) cytoskeleton is critical to numerous physical cellular processes, including cell adhesion, migration and division. Each of these processes require precise regulation of cell shape and mechanical force generation which, to a large degree, is regulated by the dynamic mechanical behaviors of a diverse assortment of F-actin networks and bundles. In this review, we review the current understanding of the mechanics of F-actin networks and identify areas of further research needed to establish physical models. We first review our understanding of the mechanical behaviors of F-actin networks reconstituted in vitro, with a focus on the nonlinear mechanical response and behavior of "active" F-actin networks. We then explore the types of mechanical response measured of cytoskeletal F-actin networks and bundles formed in living cells and identify how these measurements correspond to those performed on reconstituted F-actin networks formed in vitro. Together, these approaches identify the challenges and opportunities in the study of living cytoskeletal matter.
Topics: Actin Cytoskeleton; Actins; Animals; Cytoskeleton; Elasticity; Humans; Microtubules; Stress, Mechanical
PubMed: 19913792
DOI: 10.1016/j.jbiomech.2009.09.003 -
Scientific Reports Jul 2020S100A6 is a low molecular weight Ca-binding protein belonging to the S100 family. Many reports indicate that in the cell S100A6 has an influence on the organization of...
S100A6 is a low molecular weight Ca-binding protein belonging to the S100 family. Many reports indicate that in the cell S100A6 has an influence on the organization of actin filaments, but so far no direct interaction between S100A6 and actin has been shown. In the present study we investigated binding of S100A6 to actin and the actin-tropomyosin complex. The analyses were performed on G- and F-actin and two tropomyosin isoforms-Tpm1.6 and Tpm1.8. Using purified proteins and a variety of biochemical approaches we have shown that, in a Ca-bound form, S100A6 directly interacts with G- and F-actin and with tropomyosin, preferentially with isoform Tpm1.8. S100A6 and tropomyosin bind to the same population of filaments and the presence of tropomyosin on the microfilament facilitates the binding of S100A6. By applying proximity ligation assay we have found that in NIH3T3 fibroblasts S100A6 forms complexes both with actin and with tropomyosin. These results indicate that S100A6, through direct interactions with actin and tropomyosin, might regulate the organization and functional properties of microfilaments.
Topics: Actin Cytoskeleton; Actins; Animals; Mice; NIH 3T3 Cells; Protein Binding; Protein Isoforms; S100 Calcium Binding Protein A6; Tropomyosin
PubMed: 32733033
DOI: 10.1038/s41598-020-69752-y -
Current Biology : CB Feb 2012The field of mechanobiology has witnessed an explosive growth over the past several years as interest has greatly increased in understanding how mechanical forces are... (Review)
Review
The field of mechanobiology has witnessed an explosive growth over the past several years as interest has greatly increased in understanding how mechanical forces are transduced by cells and how cells migrate, adhere and generate traction. Actin, a highly abundant and anomalously conserved protein, plays a large role in forming the dynamic cytoskeleton that is so essential for cell form, motility and mechanosensitivity. While the actin filament (F-actin) has been viewed as dynamic in terms of polymerization and depolymerization, new results suggest that F-actin itself may function as a highly dynamic tension sensor. This property may help explain the unusual conservation of actin's sequence, as well as shed further light on actin's essential role in structures from sarcomeres to stress fibers.
Topics: Actin Cytoskeleton; Actins; Mechanotransduction, Cellular; Models, Molecular; Protein Structure, Tertiary
PubMed: 22321312
DOI: 10.1016/j.cub.2011.12.010 -
International Journal of Molecular... Oct 2022The actin cytoskeleton lies at the heart of many essential cellular processes. There are hundreds of proteins that cells use to control the size and shape of actin... (Review)
Review
The actin cytoskeleton lies at the heart of many essential cellular processes. There are hundreds of proteins that cells use to control the size and shape of actin cytoskeletal networks. As such, various pathogens utilize different strategies to hijack the infected eukaryotic host actin dynamics for their benefit. These include the control of upstream signaling pathways that lead to actin assembly, control of eukaryotic actin assembly factors, encoding toxins that distort regular actin dynamics, or by encoding effectors that directly interact with and assemble actin filaments. The latter class of effectors is unique in that, quite often, they assemble actin in a straightforward manner using novel sequences, folds, and molecular mechanisms. The study of these mechanisms promises to provide major insights into the fundamental determinants of actin assembly, as well as a deeper understanding of host-pathogen interactions in general, and contribute to therapeutic development efforts targeting their respective pathogens. This review discusses mechanisms and highlights shared and unique features of actin assembly by pathogen effectors that directly bind and assemble actin, focusing on eukaryotic actin nucleator functional mimics Sca2 (formin mimic), BimA (Ena/VASP mimic), and VopL (tandem WH2-motif mimic).
Topics: Actin Cytoskeleton; Actins; Eukaryota; Eukaryotic Cells; Formins
PubMed: 36232907
DOI: 10.3390/ijms231911606 -
Biophysical Journal Oct 2021We used computational methods to analyze the mechanism of actin filament nucleation. We assumed a pathway where monomers form dimers, trimers, and tetramers that then...
We used computational methods to analyze the mechanism of actin filament nucleation. We assumed a pathway where monomers form dimers, trimers, and tetramers that then elongate to form filaments but also considered other pathways. We aimed to identify the rate constants for these reactions that best fit experimental measurements of polymerization time courses. The analysis showed that the formation of dimers and trimers is unfavorable because the association reactions are orders of magnitude slower than estimated in previous work rather than because of rapid dissociation of dimers and trimers. The 95% confidence intervals calculated for the four rate constants spanned no more than one order of magnitude. Slow nucleation reactions are consistent with published high-resolution structures of actin filaments and molecular dynamics simulations of filament ends. One explanation for slow dimer formation, which we support with computational analysis, is that actin monomers are in a conformational equilibrium with a dominant conformation that cannot participate in the nucleation steps.
Topics: Actin Cytoskeleton; Actins; Cytoskeleton; Kinetics; Polymerization
PubMed: 34509503
DOI: 10.1016/j.bpj.2021.09.006 -
Current Biology : CB Aug 2018Coordination between actin filaments and microtubules is critical to complete important steps during cell division. For instance, cytoplasmic actin filament dynamics...
Coordination between actin filaments and microtubules is critical to complete important steps during cell division. For instance, cytoplasmic actin filament dynamics play an active role in the off-center positioning of the spindle during metaphase I in mouse oocytes [1-3] or in gathering the chromosomes to ensure proper spindle formation in starfish oocytes [4, 5], whereas cortical actin filaments control spindle rotation and positioning in adherent cells or in mouse oocytes [6-9]. Several molecular effectors have been found to facilitate anchoring between the meiotic spindle and the cortical actin [10-14]. In vitro reconstitutions have provided detailed insights in the biochemical and physical interactions between microtubules and actin filaments [15-20]. Yet how actin meshwork architecture affects microtubule dynamics is still unclear. Here, we reconstituted microtubule aster in the presence of a meshwork of actin filaments using confined actin-intact Xenopus egg extracts. We found that actin filament branching reduces the lengths and growth rates of microtubules and constrains the mobility of microtubule asters. By reconstituting the interaction between dynamic actin filaments and microtubules in a minimal system based on purified proteins, we found that the branching of actin filaments is sufficient to block microtubule growth and trigger microtubule disassembly. In a further exploration of Xenopus egg extracts, we found that dense and static branched actin meshwork perturbs monopolar spindle assembly by constraining the motion of the spindle pole. Interestingly, monopolar spindle assembly was not constrained in conditions supporting dynamic meshwork rearrangements. We propose that branched actin filament meshwork provides physical barriers that limit microtubule growth.
Topics: Actin Cytoskeleton; Actins; Animals; Microtubules; Oocytes; Xenopus laevis
PubMed: 30100343
DOI: 10.1016/j.cub.2018.06.028 -
The Journal of Biological Chemistry Jul 2015Cell physiological processes require the regulation and coordination of both mechanical and dynamical properties of the actin cytoskeleton. Here we review recent... (Review)
Review
Cell physiological processes require the regulation and coordination of both mechanical and dynamical properties of the actin cytoskeleton. Here we review recent advances in understanding the mechanical properties and stability of actin filaments and how these properties are manifested at larger (network) length scales. We discuss how forces can influence local biochemical interactions, resulting in the formation of mechanically sensitive dynamic steady states. Understanding the regulation of such force-activated chemistries and dynamic steady states reflects an important challenge for future work that will provide valuable insights as to how the actin cytoskeleton engenders mechanoresponsiveness of living cells.
Topics: Actin Cytoskeleton; Actins; Animals; Biomechanical Phenomena; Humans; Models, Molecular; Protein Structure, Tertiary
PubMed: 25957404
DOI: 10.1074/jbc.R115.636472 -
Trends in Biochemical Sciences May 2023Actin, one of the most abundant proteins in nature and a key component of the cytoskeleton, undergoes a unique multistep N-terminal (Nt) maturation. In a recent report,...
Actin, one of the most abundant proteins in nature and a key component of the cytoskeleton, undergoes a unique multistep N-terminal (Nt) maturation. In a recent report, Haahr et al. identified actin maturation protease (ACTMAP) as the dedicated actin aminopeptidase and showed that its absence is associated with abnormal muscle physiology.
Topics: Actins; Cytoskeleton; Actin Cytoskeleton
PubMed: 36804256
DOI: 10.1016/j.tibs.2023.02.002 -
Journal of Biosciences 2023Eukaryotic cell migration requires continuous supply of actin polymers at the leading edges to make and extend lamellipodia or pseudopodia. Linear and branched... (Review)
Review
Eukaryotic cell migration requires continuous supply of actin polymers at the leading edges to make and extend lamellipodia or pseudopodia. Linear and branched filamentous actin polymers fuel cell migration. Branching of actin polymers in the lamellipodia/pseudopodia is facilitated by the actin-related protein (Arp) 2/3 complex, whose function is essentially controlled by the Scar/WAVE complex. In cells, the Scar/WAVE complex remains inactive, and its activation is a highly regulated and complex process. In response to signalling cues, GTP-bound Rac1 associates with Scar/WAVE and causes activation of the complex. Rac1 is essential but not sufficient for the activation of the Scar/ WAVE complex, and it requires multiple regulators, such as protein interactors and modifications (phosphorylation, ubiquitylation, etc.). Although our understanding of the regulation of the Scar/WAVE complex has improved over the last decade, it remains enigmatic. In this review, we have provided an overview of actin polymerization and discussed the importance of various regulators of Scar/WAVE activation.
Topics: Actin Cytoskeleton; Actins; Cell Movement; rac1 GTP-Binding Protein
PubMed: 37204155
DOI: No ID Found -
FEBS Letters Apr 2013Vinculin, and its splice variant metavinculin, are scaffolding proteins that localize to cellular adhesions. Vinculin is a key player in mediating cell adhesion,... (Review)
Review
Vinculin, and its splice variant metavinculin, are scaffolding proteins that localize to cellular adhesions. Vinculin is a key player in mediating cell adhesion, motility, and cellular response to force. In the past decade, a number of new studies have evaluated the importance of vinculin oligomers, especially in their role of bundling F-actin. Emerging evidence also suggests that vinculin oligomerization is important for vinculin's scaffolding function. Here we describe the latest findings on vinculin's interaction with F-actin and we clarify the different known vinculin oligomers. Differences in these functions between vinculin and metavinculin provide key insights to the structure and function of these oligomers, and should guide further studies.
Topics: Actin Cytoskeleton; Actins; Humans; Models, Molecular; Protein Binding; Protein Multimerization; Protein Structure, Tertiary; Vinculin
PubMed: 23466368
DOI: 10.1016/j.febslet.2013.02.042