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International Journal of Molecular... Jun 2018In muscle, but not in single-molecule mechanics studies, actin, myosin and accessory proteins are incorporated into a highly ordered myofilament lattice. In view of this... (Review)
Review
In muscle, but not in single-molecule mechanics studies, actin, myosin and accessory proteins are incorporated into a highly ordered myofilament lattice. In view of this difference we compare results from single-molecule studies and muscle mechanics and analyze to what degree data from the two types of studies agree with each other. There is reasonable correspondence in estimates of the cross-bridge power-stroke distance (7⁻13 nm), cross-bridge stiffness (~2 pN/nm) and average isometric force per cross-bridge (6⁻9 pN). Furthermore, models defined on the basis of single-molecule mechanics and solution biochemistry give good fits to experimental data from muscle. This suggests that the ordered myofilament lattice, accessory proteins and emergent effects of the sarcomere organization have only minor modulatory roles. However, such factors may be of greater importance under e.g., disease conditions. We also identify areas where single-molecule and muscle data are conflicting: (1) whether force generation is an Eyring or Kramers process with just one major power-stroke or several sub-strokes; (2) whether the myofilaments and the cross-bridges have Hookean or non-linear elasticity; (3) if individual myosin heads slip between actin sites under certain conditions, e.g., in lengthening; or (4) if the two heads of myosin cooperate.
Topics: Actin Cytoskeleton; Actins; Actomyosin; Animals; Isometric Contraction; Muscle Contraction; Muscle Fibers, Skeletal; Myofibrils; Myosins
PubMed: 29941816
DOI: 10.3390/ijms19071863 -
Current Opinion in Cell Biology Feb 2011In cells the de novo nucleation of actin filaments from monomers requires actin-nucleating proteins. These fall into three main families--the Arp2/3 complex and its... (Review)
Review
In cells the de novo nucleation of actin filaments from monomers requires actin-nucleating proteins. These fall into three main families--the Arp2/3 complex and its nucleation promoting factors (NPFs), formins, and tandem-monomer-binding nucleators. In this review, we highlight recent advances in understanding the molecular mechanism of actin nucleation by both well-characterized and newly identified nucleators, and explore current insights into their cellular functions in membrane trafficking, cell migration and division. The mechanisms and functions of actin nucleators are proving to be more complex than previously considered, with extensive cooperation and overlap in their cellular roles.
Topics: Actin Cytoskeleton; Actins; Animals; Cell Division; Cell Movement; Cells; Humans; Models, Biological
PubMed: 21093244
DOI: 10.1016/j.ceb.2010.10.007 -
Seminars in Cell & Developmental Biology Jun 2020Actin filaments (F-actin) are a key component of eukaryotic cells. Whether serving as a scaffold for myosin or using their polymerization to push onto cellular... (Review)
Review
Actin filaments (F-actin) are a key component of eukaryotic cells. Whether serving as a scaffold for myosin or using their polymerization to push onto cellular components, their function is always related to force generation. To control and fine-tune force production, cells have a large array of actin-binding proteins (ABPs) dedicated to control every aspect of actin polymerization, filament localization, and their overall mechanical properties. Although great advances have been made in our biochemical understanding of the remodeling of the actin cytoskeleton, the structural basis of this process is still being deciphered. In this review, we summarize our current understanding of this process. We outline how ABPs control the nucleation and disassembly, and how these processes are affected by the nucleotide state of the filaments. In addition, we highlight recent advances in the understanding of actomyosin force generation, and describe recent advances brought forward by the developments of electron cryomicroscopy.
Topics: Actin Cytoskeleton; Animals; Humans; Models, Molecular; Molecular Structure
PubMed: 31836290
DOI: 10.1016/j.semcdb.2019.11.018 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2018Cytokinesis and single-cell wound repair both involve contractile assemblies of filamentous actin (F-actin) and myosin II organized into characteristic ring-like arrays.... (Review)
Review
Cytokinesis and single-cell wound repair both involve contractile assemblies of filamentous actin (F-actin) and myosin II organized into characteristic ring-like arrays. The assembly of these actomyosin contractile rings (CRs) is specified spatially and temporally by small Rho GTPases, which trigger local actin polymerization and myosin II contractility via a variety of downstream effectors. We now have a much clearer view of the Rho GTPase signaling cascade that leads to the formation of CRs, but some factors involved in CR positioning, assembly, and function remain poorly understood. Recent studies show that this regulation is multifactorial and goes beyond the long-established Ca -dependent processes. There is substantial evidence that the Ca -independent changes in cell shape, tension, and plasma membrane composition that characterize cytokinesis and single-cell wound repair also regulate CR formation. Elucidating the regulation and mechanistic properties of CRs is important to our understanding of basic cell biology and holds potential for therapeutic applications in human disease. In this review, we present a primer on the factors influencing and regulating CR positioning, assembly, and contraction as they occur in a variety of cytokinetic and single-cell wound repair models. Anat Rec, 301:2051-2066, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Actin Cytoskeleton; Actomyosin; Animals; Cell Membrane; Contractile Proteins; Cytokinesis; Humans; Tissue Scaffolds; Wound Healing
PubMed: 30312008
DOI: 10.1002/ar.23962 -
Biophysical Journal Apr 2008The mechanical properties of cytoskeletal actin bundles play an essential role in numerous physiological processes, including hearing, fertilization, cell migration, and...
The mechanical properties of cytoskeletal actin bundles play an essential role in numerous physiological processes, including hearing, fertilization, cell migration, and growth. Cells employ a multitude of actin-binding proteins to actively regulate bundle dimensions and cross-linking properties to suit biological function. The mechanical properties of actin bundles vary by orders of magnitude depending on diameter and length, cross-linking protein type and concentration, and constituent filament properties. Despite their importance to cell function, the molecular design principles responsible for this mechanical behavior remain unknown. Here, we examine the mechanics of cytoskeletal bundles using a molecular-based model that accounts for the discrete nature of constituent actin filaments and their distinct cross-linking proteins. A generic competition between filament stretching and cross-link shearing determines three markedly different regimes of mechanical response that are delineated by the relative values of two simple design parameters, revealing the universal nature of bundle-bending mechanics. In each regime, bundle-bending stiffness displays distinct scaling behavior with respect to bundle dimensions and molecular composition, as observed in reconstituted actin bundles in vitro. This mechanical behavior has direct implications on the physiological bending, buckling, and entropic stretching behavior of cytoskeletal processes, as well as reconstituted actin systems. Results are used to predict the bending regimes of various in vivo cytoskeletal bundles that are not easily accessible to experiment and to generate hypotheses regarding implications of the isolated behavior on in vivo bundle function.
Topics: Actin Cytoskeleton; Biomechanical Phenomena; Computer Simulation; Cytoskeleton; Elasticity; Models, Chemical; Models, Molecular; Molecular Conformation; Stress, Mechanical
PubMed: 18055529
DOI: 10.1529/biophysj.107.119743 -
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 -
Developmental Cell Dec 2014Cytokinesis mediates the physical separation of dividing cells after chromosome segregation. In animal cell cytokinesis, a contractile ring, mainly composed of actin and... (Review)
Review
Cytokinesis mediates the physical separation of dividing cells after chromosome segregation. In animal cell cytokinesis, a contractile ring, mainly composed of actin and myosin filaments, ingresses a cleavage furrow midway between the two spindle poles. A distinct machinery, involving the endosomal sorting complex required for transport III (ESCRT-III), subsequently splits the plasma membrane of nascent daughter cells in a process termed abscission. Here, we provide a brief overview of early cytokinesis events in animal cells and then cover in depth recently emerging models for the assembly and function of the abscission machinery and its temporal coordination with chromosome segregation.
Topics: Actin Cytoskeleton; Animals; Cell Membrane; Cell Proliferation; Chromosome Segregation; Cytokinesis; Endosomal Sorting Complexes Required for Transport; Humans
PubMed: 25490264
DOI: 10.1016/j.devcel.2014.11.006 -
Journal of Smooth Muscle Research =... Dec 2004The Ca2+-dependent, reversible phosphorylation of the 20 kDa regulatory myosin light chain (MLC) plays a primary role in regulating the contraction of smooth muscle.... (Review)
Review
The Ca2+-dependent, reversible phosphorylation of the 20 kDa regulatory myosin light chain (MLC) plays a primary role in regulating the contraction of smooth muscle. However, it is well known that the Ca2+ signal is not the only factor which regulates such contraction, however, the alteration of the Ca2+ sensitivity in the contractile apparatus is also known to play an important role. The degree of MLC phosphorylation is determined by the balance of the activity between phosphorylation and dephosphorylation. Either the Ca2+-independent activation of MLC phosphorylation or the inhibition of MLC dephosphorylation causes a greater MLC phosphorylation for a given level of Ca2+ signal and thereby potentiates the myofilament Ca2+ sensitivity. The smooth muscle myosin light chain phosphatase (MLCP) consisting of three subunits was first isolated and cloned in the early '90s. The intensive investigation thereafter has uncovered the biochemical basis for regulating the activity of MLCP. The regulation of the MLCP activity is now considered to play a critical role in regulating the myofilament Ca2+ sensitivity. There are three major mechanisms in the regulation of MLCP; (1) the phosphorylation of a 110 kDa regulatory subunit of MLCP (2) the conformational change of the trimeric structure, and (3) the inhibition by a smooth muscle specific inhibitor protein, CPI-17. Furthermore, some kinases have been found to phosphorylate the MLC and activate the contraction of smooth muscle in a Ca2+-independent manner. Numerous protein kinases have been found to be involved in the regulation of MLC phosphorylation, and rho-kinase is one of the most frequently investigated kinases. The smooth muscle physiology is now asked to integrate the current understanding of the biochemical mechanisms and to clarify which kinases and/or proteins in the contractile apparatus play a physiological role in regulating the myofilament Ca2+ sensitivity and how such extracellular contractile stimulation modulates these mechanisms.
Topics: Actin Cytoskeleton; Animals; Calcium; Humans; Muscle, Smooth, Vascular; Myosins; Phosphorylation
PubMed: 15725705
DOI: 10.1540/jsmr.40.219 -
Journal of Plant Research Mar 2017ACTIN DEPOLYMERIZING FACTOR (ADF) is a conserved protein among eukaryotes. The main function of ADF is the severing and depolymerizing filamentous actin (F-actin), thus... (Review)
Review
ACTIN DEPOLYMERIZING FACTOR (ADF) is a conserved protein among eukaryotes. The main function of ADF is the severing and depolymerizing filamentous actin (F-actin), thus regulating F-actin organization and dynamics and contributing to growth and development of the organisms. Mammalian genomes contain only a few ADF genes, whereas angiosperm plants have acquired an expanding number of ADFs, resulting in the differentiation of physiological functions. Recent studies have revealed functions of ADFs in plant growth and development, and various abiotic and biotic stress responses. In biotic stress responses, ADFs are involved in both susceptibility and resistance, depending on the pathogens. Furthermore, recent studies have highlighted a new role of ADF in the nucleus, possibly in the regulation of gene expression. In this review, I will summarize the current status of plant ADF research and discuss future research directions.
Topics: Actin Cytoskeleton; Destrin; Plant Proteins; Plants
PubMed: 28044231
DOI: 10.1007/s10265-016-0899-8 -
International Journal of Molecular... May 2022The actin containing tropomyosin and troponin decorated thin filaments form one of the crucial components of the contractile apparatus in muscles. The thin filaments are... (Review)
Review
The actin containing tropomyosin and troponin decorated thin filaments form one of the crucial components of the contractile apparatus in muscles. The thin filaments are organized into densely packed lattices interdigitated with myosin-based thick filaments. The crossbridge interactions between these myofilaments drive muscle contraction, and the degree of myofilament overlap is a key factor of contractile force determination. As such, the optimal length of the thin filaments is critical for efficient activity, therefore, this parameter is precisely controlled according to the workload of a given muscle. Thin filament length is thought to be regulated by two major, but only partially understood mechanisms: it is set by (i) factors that mediate the assembly of filaments from monomers and catalyze their elongation, and (ii) by factors that specify their length and uniformity. Mutations affecting these factors can alter the length of thin filaments, and in human cases, many of them are linked to debilitating diseases such as nemaline myopathy and dilated cardiomyopathy.
Topics: Actin Cytoskeleton; Actins; Humans; Muscle Contraction; Sarcomeres; Tropomyosin
PubMed: 35628117
DOI: 10.3390/ijms23105306