Cell Actin-like microfilaments

Just as myosins are able to move along microfilaments, there are motor proteins that move along microtubules. Microtubules, like microfilaments, are polar polymeric assemblies, but unlike actin-myosin interactions, microtubule-based motors exist that move along microtubules in either direction. A constant traffic of vesicles and organelles is visible in cultured cells especially using time-lapse photography. The larger part of this movement takes place on micrombules and is stimulated by phorbol ester (an activator of protein kinase C), and over-expression of N-J aj oncoprotein (Alexandrova et al., 1993). 

Two major types of muscle fibers are found in humans white (anaerobic) and red (aerobic). The former are particularly used in sprints and the latter in prolonged aerobic exercise. During a sprint, muscle uses creatine phosphate and glycolysis as energy sources in the marathon, oxidation of fatty acids is of major importance during the later phases. Nonmuscle cells perform various types of mechanical work carried out by the structures constituting the cytoskeleton. These strucmres include actin filaments (microfilaments), micrombules (composed primarily of a- mbulin and p-mbulin), and intermediate filaments. The latter include keratins, vimentin-like proteins, neurofilaments, and lamins. 

A direct link between cytochalasin and actin was provided by the demonstration that cytochalasin decreases the viscosity of actin filaments purified from muscle (50). This experiment led to two important conclusions. First, cytochalasin interacts directly with actin. Second, an interaction of cytochalasin with actin or actin-like proteins in vivo could account for the ability of cytochalasin to inhibit various forms of cell motility and contraction (50). Thus, actin was shown to be the molecular target of cytochalasin and implicated as a critical component of the microfilaments involved in cytochalasin-sensitive processes, including contraction of the cleavage furrow at cytokinesis. 

Thread-like actin filaments (microfilaments) spread through the hepatocytes creating a three-dimensional network and ensuring both form and stability of the cell. They also guarantee the shape of the microvilli and fenestrae as well as supporting the mechanical functions of the canaliculi. In addition, they influence the viscosity of the cytoplasm. Cytochalasin A depolymerizes... 

Microfilaments - smallest of the three, they are made of actin and small amounts of myosin (like in muscle tissue). They function in cell movement like cytoplasmic streaming, endocytosis, and ameboid movement. This structure pinches the two cells apart after cell division, forming two new cells. 

The force which propels secretory granules along the microtubules is less clear. It is known that the micro tubular system exists in at least two states the fully polymerized form represented by intact microtubules, and the disintegrated form represented by a pool of depolymer-ized globular proteins (tubulin) in the cytoplasm. In order for microtubules to function properly, a dynamic state of equilibrium must exist between the fully-formed tubules and the tubule constituent pool. Thus, colchicine and other antimitotic agents bind to specific sites on the microtubular subunits. It has been proposed that they exert their effect by inactivating the free subunits and thereby shift the equilibrium between the associated and dissociated states of the microtubules so that eventually no intact microtubules remain and secretion is inhibited. Similarly, stabilization of microtubules in the polymerized form with D2O also inhibits cellular secretion of insulin. From this, one can hypothesize that if the secretory vesicles were somehow attached to the microtubules, possibly by way of microfilaments, a constant cycle of depolymerization near the cell periphery, with a repolymerization at the central area of the cell, would advance the secretory vesicle from the cell center to the cell web. In addition, if tubulin actually contains an actin-like contractile protein, then this contractile property may well contribute to the intracellular movement of secretory materials. 

Microfilaments of F actin traverse the microvilli in ordered bundles. The microfila-ments are attached to each other by actin-as-sociated proteins, particularly fimbrin and vil-lin. Calmodulin and a myosin-like ATPase connect the microfilaments laterally to the plasma membrane. Fodrin, another microfila-ment-associated protein, anchors the actin fibers to each other at the base, as well as attaching them to the cytoplasmic membrane and to a network of intermediate filaments. In this example, the microfilaments have a mainly static function. In other cases, actin is also involved in dynamic processes. These include muscle contraction (see p. 332), cell movement, phagocytosis by immune cells, the formation of microspikes and lamellipo-dia (cellular extensions), and the acrosomal process during the fusion of sperm with the egg cell. 

II.B.2). Sphinxolide (40) was revealed, like scytophycins, to cause rapid loss of microfilaments in cultured cells and potently inhibit actin polymerization in vitro. Sphinxolide (40) was also shown to circumvent multidrug resistance mediated by overexpression of either P-glycoprotein or MRP [91]. 

---