Actin-containing microfilaments

Brody AR, Hill LH, Stirewalt WS, Adler KB. Actin-containing microfilaments of pulmonary epithelial cells provide a mechanism for translocating asbestos to the interstitium. Chest 1993 5 11-12. 

The ability of a cell to hold or to change shape and to move organelles within it depends on the existence of a cytoskeleton, comprising actin filaments (microfilaments), microtubules, and intermediate filaments (IPs) capable of transmitting force. Actin filaments and microtubules contain predominantly actin and tubulin, respectively. (Table 21-1). The diameter of intermediate filaments (10 nm) is between that of actin filaments (6-7 nm) and microtubules (25 nm). They are structural proteins not directly involved in motion. 

The cytoskeleton also contains different accessory proteins, which, in accordance with their affinities and functions, are designated as microtubule-associated proteins (MAPs), actin-binding proteins (ABPs), intermediate-filament-associated proteins (IFAPs), and myosin-binding proteins. This chapter is focused on those parts of the cytoskeleton that are composed of microfilaments and microtubules and their associated proteins. The subject of intermediate filaments is dealt with in detail in Volume 2. 

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. 

Nonmuscle Cells Contain Actin That Forms Microfilaments... 

Actin filaments grow rapidly within cells, and the clearest evidence of this rapid growth is the ability of the cell s leading edge to move at rates of 0.5 to 1 micrometer per second. Likewise, actin-based motility of Listeria and Shigella can attain rates of nearly 0.5 micrometers per second. Because microfilaments contain about 360 actin monomers per micrometer of length, a motility rate of 0.5 to 1 micrometer per second corresponds to an apparent first-order rate constant (/.e., / apparent = on [Actin-ATP]) of about 180-360 s . The bimolecular rate constant for actin-ATP addition to the barbed end has a nominal value of 2-3 X 10 s . Therefore, one can estimate... 

Li, Y., Hua, F., Carraway, K.L., and Carothers Carraway, C.A. 1999. The pl85" -contain-ing glycoprotein complex of a microfilament-associated signal transduction particle. Purification, reconstitution, and molecular associations with p58 and actin. J Biol Chem 274(36) 25651-25658. 

The cytosol of a eukaryotic cell contains three types of filaments that can be distinguished on the bases of their diameter, type of subunit, and subunit arrangment (Figure 5-29). Actin filaments, also called microfilaments, are 8-9 nm in diameter and have a twisted two-stranded structure. Microtubules are hollow tubelike structures, 24 nm in diameter, whose walls are formed by adjacent protofilaments. Intermediate filaments (IFs) have the structure of a 10-nm-dlameter rope. 

Actin exists as a globular monomer called G-actin and as a filamentous polymer called F-actin, which is a linear chain of G-actin subunits. (The microfilaments visualized in a cell by electron microscopy are F-actin filaments plus any bound proteins.) Each actin molecule contains a Mg " ion complexed with either ATP or ADR Thus there are four states of actin ATP-G-actin, ADP-G-actin, ATP-F-actin, and ADP-F-actin. Two of these forms, ATP-G-actin and ADP-F-actin, predominate in a cell. The importance of the interconversion between the ATP and the ADP forms of actin in the assembly of the cytoskeleton is discussed later. 

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. 

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