Actin filament, structure

Role of the Cytoskeleton in Cell Division Formation of the Mitotic Spindle, Mitosis, and Cytokinesis Drug Effects on Microtubules Mlcrofllaments Actin Filaments Structure and Composition... 

The diversity of these subcellular actin structures is remarkable and appears to be determined by the interactions of many actin-binding proteins (ABPs) as well as by changes in the concentrations of intracellular signaling molecules such as Ca and cAMP, by small GTP-binding proteins, and by signals arising from mechanical stress. Approximately 50% of the actin molecules in most animal cells are unpolymerized subunits in the cytosolic pool and exist in a state of dynamic equilibrium with labile F-actin filamentous structures (i.e., new structures are formed while existing structures are renewed) (Hall, 1994). 

III. Actin Filament Structure and the Z-Band A. The Actin Monomer... 

As in the case of the myosin head, knowledge of actin filament structure, or thin filament structure as it is termed when tropomyosin and troponin are present, also progressed rapidly when the structure of the globular actin (G-actin) monomer was determined by protein crystallography in... 

FIGURE 4 Schematic depicting the potential roles for MAPK in contractile versus proliferative (or cultured) smooth muscle. MAPK is activated in response to stimulation by growth factors, stretch, and pharmacological agents. This process can be inhibited by cAMP and cAMP-dependent protein kinase. Once activated, MAPK phos-phorylates a number of intracellular proteins (both cytoplasmic and nuclear) that result in an alteration of growth and proliferation in cultured cells. In contractile smooth muscle, MAPK phosphorylation of caldesmon may lead to alterations in muscle contractility or actin filament structure. 

Using a micropipette and a small suction pressure to aspirate a hemispherical projection from a cell body into the pipette, Evans and Yeung measured a value for the cortical tension of 0.035 mN/m. Needham and Eiochmuth [1992] measured the cortical tension of individual cells that were driven down a tapered pipette in a series of equilibrium positions. In many cases the cortical tension increased as the cell moved further into the pipette, which means that the ceU has an apparent area expansion modulus (Equation 60.7). They obtained an average value of 0.04 mN/m for the expansion modulus and an extrapolated value for the cortical tension (at zero area dilation) in the resting state of 0.024 mN/m. The importance of the actin cytoskeleton in maintaining cortical tension was demonstrated by Tsai et al. [ 1994]. Treatment of the cells with a drug that disrupts actin filament structure (CTB = cytochalasin B) resulted in a decrease in cortical tension from 0.027 to 0.022 mN/m at a CTB concentration of 3 /rM and to 0.014 mN/m at 30 /rM. 

The F-actin helix has 13 molecules of G-actin in six turns of the helix, repeating every 360 A. Oriented gels of actin fibers yield x-ray fiber diffraction patterns to about 6 A resolution. Knowing the atomic structure of G-actin it was possible for the group of Ken Holmes to determine its orientation in the F-actin fiber, and thus arrive at an atomic model of the actin filament that best accounted for the fiber diffraction pattern. 

The structure and arrangement of the actin and myosin filaments in muscle. During muscle contraction the cyclic interaction of myosin crossbridges with actin filaments draws the actin filaments across the myosin filaments. 

More than 50 proteins have been discovered in the cytosol of nonmuscle cells that bind to actin and affect the assembly and disassembly of actin filaments or the cross-linking of actin filaments with each other, with other filamentous components of the cytoskeleton, or with the plasma membrane. Collectively, these are known as actin-binding proteins (ABPs). Their mechanisms of actions are complex and are subject to regulation by specific binding affinities to actin and other molecules, cooperation or competition with other ABPs, local changes in the concentrations of ions in the cytosol, and physical forces (Way and Weeds, 1990). Classifications of ABPs have been proposed that are based on their site of binding to actin and on their molecular structure and function (Pollard and Cooper, 1986 Herrmann, 1989 Pollard et al., 1994). These include the following ... 

Fibronectin receptor is a two-chain glycoprotein of the integrin family that serves as a transmembrane linker by binding to talin on the cytoplasmic side and to fibronectin on the external side of the membrane. The pull exerted by stress fibers on attached structures may be produced by bipolar assemblies of nonmuscle myosin molecules producing a sliding of actin filaments of opposite polarity. 

The structure of the contractile apparatus of smooth muscle at the next higher level is also characteristically different from other muscles. The concentrations of actin and myosin in smooth muscle are about three times higher for actin and four times lower for myosin than in skeletal muscle. Correspondingly, in smooth muscle the ratio of the numbers of moles of actin to moles of myosin, and the ratio of the number of actin filaments to those of myosin filaments, are about 12 times larger than for other muscles. Thus, the arrangements of the two sets of filaments are bound to be quite different just on the basis of numbers of actin and myosin... 

In order to exert a force from one end of a muscle to the other, a structure must be continuous from one end to the other. In smooth muscle tissue, this structure is a system of alternating myosin and actin filaments within a cell, firm attachments first to the cell membrane, and beyond that extracellular attachments to the... 

Actin is a 42 kDa bent dumbbell-shaped globular monomer which is found in most eukaryotic cells. It is the primary protein of the thin (or actin) filaments. Also, by mass or molarity, actin is the largest constituent of the contractile apparatus, actually reaching millimolar concentrations. Actins from different sources seem to be more similar than myosins from the same sources. Actin binds ATP which is hydrolyzed to ADP, if the monomeric actin polymerizes. The backbone structure of the actin filament is a helix formed by two linear strands of polymerized actins like two strings of actin beads entwined. 

Organization into macromolecular structures. There are no apparent templates necessary for the assembly of muscle filaments. The association of the component proteins in vitro is spontaneous, stable, and relatively quick. Filaments will form in vitro from the myosins or actins from all three kinds of muscle. Yet in vitro smooth muscle myosin filaments are found to be stable only in solutions somewhat different from in vivo conditions. The organizing principles which govern the assembly of myosin filaments in smooth muscle are not well understood. It is clear, however, a filament is a sturdy structure and that individual myosin molecules go in and out of filaments whose structure remains in a functional steady-state. As described above, the crossbridges sticking out of one side of a smooth muscle myosin filament are all oriented and presumably all pull on the actin filament in one direction along the filament axis, while on the other side the crossbridges all point and pull in the opposite direction. The complement of minor proteins involved in the structure of the smooth muscle myosin filament is unknown, albeit not the same as that of skeletal muscle since C-protein and M-protein are absent. 

The superstructure of smooth muscle actin filaments is differentiated from those of striated muscle by the absence of the troponins and the lateral organization by association of the filaments with dense bodies instead of with the Z-line. How these differences are encoded is again not at all clear. However, the myofibrillar structure and the alignment of the alternating actin and myosin filaments is apparently due primarily to dense bodies and the actin-actinin macrostructures. As the bent dumbbell shaped actins assemble into filaments they are all oriented in the same direction. The S-1 fragments of myosin will bind to actin filaments in vitro and in... 

Nonmuscle cells perform mechanical work, including self-propulsion, morphogenesis, cleavage, endocytosis, exocytosis, intracellular transport, and changing cell shape. These cellular functions are carried out by an extensive intracellular network of filamentous structures constimting the cytoskeleton. The cell cytoplasm is not a sac of fluid, as once thought. Essentially all eukaryotic cells contain three types of filamentous struc-mres actin filaments (7-9.5 nm in diameter also known as microfilaments), microtubules (25 nm), and intermediate filaments (10-12 nm). Each type of filament can be distinguished biochemically and by the electron microscope. 

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