Microfilaments cellular function

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. 

The multifimctional CaM kinases are collectively referred to as CaM kinases of type II, whereby further subtypes a, p, y and 6 are differentiated. The a and P subtypes of CaM kinase II only occur in the brain whereas the other subtypes are also found in other organs. The multifunctional CaM kinases regulate many processes (see Table 7.1) such as glycogen metabolism, activity of transcription factors, microfilament formation, synaptic release of neurotransmitters from storage vesicles, biosynthesis of neurotransmitters and many more. An important cellular function is assigned to CaM kinase II in brain, where it makes up 0.25 % of the total protein. 

IF proteins assemble into a filament with a diameter of 8-12 nm which is the intermediate size between those of microtubules (25 nm) and microfilaments (7-9 nm). Whereas microtubules and microfilaments are more likely to be related to many basic cellular functions [44, 45], intermediate filaments play a key role in mechanical properties of tissues and cells, such as the stiffness and maximum strain, and the mechanical integrity of various tissues such as muscle, liver, and skin [44, 46]. 

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. 

Dendrites are the (filamentous) terminal portions of neuron that bind neurotransrrritter chemicals migrating across the synaptic gaps separating neurons. Depending on the type and function of a particular neuron, neurotransmitters may cause or inhibit the transmission of neural impulses. The cell body contains the cell nucleus and a concentration of cellular organelles. The cell body is the site of the normal metabolic reactions that allow the cell to remain viable. Neurotransmitters synthesized within the cell body are transported to the axon terminus by microfilaments and microtubules. 

Pollard TD, Almo S, Quirk S etal. (1994) Structure of actin binding proteins Insights about function at atomic resolution. In Annu. Rev. Cell Biol. 10 207-49 Popoff MR, Rubin EJ, Gill DM et al. (1988) Actin-specific ADP-ribosyltransferase produced by a Clostridium difficile strain. In Infect. Immun. 56 2299-306 Popoff MR, Boquet P (1988) Clostridium spiroforme toxin is a binary toxin which ADP-ribosylates cellular actin. In Biochem. Biophys. Res. Commun. 152 1361—8 Reuner KH, Presek P, Boschek CB et al. (1987) Botulinum C2 toxin ADP-ribosylates actin and disorganizes the microfilament network in intact cells. In Eur. J. Cell Biol. 43 134-40... 

The use of bacterial toxins as molecular probes will continue to provide valuable information on the functions of their various substrates. In addition, studies on endogenous cellular mono(ADP-ribosyl) transferases look set to expand. New substrates will be identified and the biochemical consequences of the different modifications will reveal the roles played by mono(ADP-ribosylation) reactions in different cell compartments. For example, the case of cytoskeletal actin has been discussed (see Figure 8). Work in Mandel s laboratory (Mandel, 1992) has revealed that other cytoskeletal proteins are also substrates for endogenous ADP-ribosyl transferase, including components of the microfilaments (tubulin, intermediate filaments, and the neurofilament proteins L, M, and H). 

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. 

---