Control of actin assembly and disassembly at filament ends

Department of Cell Biology, Washington University, Box 8228, St Louis, MO 631110, USA.
Current Opinion in Cell Biology (Impact Factor: 8.47). 03/2000; 12(1):97-103. DOI: 10.1016/S0955-0674(99)00062-9
Source: PubMed


The most important discovery in the field is that the Arp2/3 complex nucleates assembly of actin filaments with free barbed ends. Arp2/3 also binds the sides of actin filaments to create a branched network. Arp2/3's nucleation activity is stimulated by WASP family proteins, some of which mediate signaling from small G-proteins. Listeria movement caused by actin polymerization can be reconstituted in vitro using purified proteins: Arp2/3 complex, capping protein, actin depolymerizing factor/cofilin, and actin. actin depolymerizing factor/cofilin increases the rate at which actin subunits leave pointed ends, and capping protein caps barbed ends.

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Available from: Dorothy A Schafer, Feb 05, 2014
    • "We analyzed the effects of P 4 in cofilin phosphorylation, which is important to induce the formation of plus actin ends [48]. The formation of the plus actin ends is essential in the dynamic remodeling of the actin cytoskeleton, since the polymerization of new actin filaments that lead to the formation of protrusions during the early stages of cell motility occurs in these ends [49]. In some studies, it has been observed that P 4 is capable of modifying cell morphology and that these events are conducted through rearrangements of the actin cytoskeleton through changes in the phosphorylation state of ABPs [25,50]. "
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    ABSTRACT: Astrocytomas are the most common and aggressive primary brain tumors in humans. Invasiveness of these tumors has been attributed in part to deregulation of cell motility-dependent cytoskeletal dynamics that involves actin-binding proteins such as cofilin. Progesterone (P4) has been found to induce migration and invasion of cells derived from breast cancer and endothelium. However, the role of P4 in migration and invasion of astrocytoma cells as well as its effects on astrocytomas cytoskeleton remodeling is not known. In this work we evaluated these aspects in D54 and U251 cells derived from human astrocytomas from the highest degree of malignancy (grade IV, glioblastoma). Our results showed that in scratch-wound assays P4 increased the number of D54 and U251 cells migrating from 3 to 48 hours. Both RU486, a P4 receptor (PR) antagonist, and an oligonucleotide antisense against PR significantly blocked P4 effects. Transwell assays showed that P4 significantly increased the number of invasive cells at 24 hours. As in the case of migration, this effect was blocked by RU486. Finally, by western blotting, an increase in the cofilin/p-cofilin ratio at 15 and 30 minutes and a decrease at 30 and 60 minutes in U251 and D54 cells, respectively, was observed after P4, P4 + RU486 and RU486 treatments. These data suggest that P4 increases human astrocytoma cells migration and invasion through its intracellular receptor, and that cofilin activation by P4 is independent of PR action.
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    • "If G-actin levels fall below the critical concentration, no more polymerization takes place. The maintenance of the actin pool necessitates the depolymerization of existing actin filaments which appears to be facilitated by different supporting proteins such as ADF and cofilin [124] [125]. "
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    ABSTRACT: Over the last decade, our understanding of the vascular endothelial growth factor (VEGF) has rapidly increased, becoming the focus of many investigations the world over. Besides its classical role in the vascular system, VEGF was also identified as a factor affecting the nervous system. One structure that responds to VEGF-signaling is the axonal growth cone, the correct behavior of which is essential for the development of a properly working neuronal network. It navigates growing axons to their final destination and helps to create proper synapses at predetermined locations. Recent data concerning the impact of VEGF on the actin cytoskeleton of neuronal growth cones are discussed and new findings of VEGF-signaling in regard to actin dynamics are specified. Overall, we describe the role of VEGF regulation of cofilin and the Arp2/3-complex in axonal growth cones.
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    • "Cell migration requires a number of changes, e.g. the reorganization of the actin cytoskeleton (Mogilner and Edelstein-Keshet, 2002), changes in cell shape and in activity of various cytokines and growth factors. On the other hand, proper organization of the cell cytoskeleton is essential for a number of fundamental processes in cells including proliferation, migration, differentiation, signal transmission or regeneration (Cooper and Schafer, 2000; Mogilner and Edelstein-Keshet, 2002; Pollard and Borisy, 2003). There are several reports indicating significant disruption of the hepatocyte actin cytoskeleton caused by MC-LR (Runnegar et al., 1995; Toivola and Eriksson, 1999; Batista et al., 2003). "
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    ABSTRACT: The occurrence of cyanobacterial toxic peptides, including microcystins (MCs), are an emerging health issue due to the eutrophication of water bodies. MCs have a strong influence on human cells, predominantly hepatocytes, however, toxicity was also observed in kidney, lung and dermal skin cells. Skin as the most external barrier of the human body is responsible for the maintenance of homeostasis of the whole organism. Simultaneously, skin cells may be the most exposed to MCs during recreational activity. The aim of this study was to examine the impact of MC-LR on processes indispensable for normal skin function and regeneration, namely, viability, migration and actin cytoskeleton organization of human keratinocytes. The results showed that short exposure to MC-LR does not affect proliferation of human skin keratinocytes but it is toxic after longer incubation in dose-dependent manner. Total disruption of the actin cytoskeleton was observed under the same MC-LR concentration. Furthermore, keratinocyte migration was inhibited at MC-LR concentrations of 50 μM after incubation for only 4 hours. Some of the negative impacts of MC-LR on the examined cell processes may be partly reversible. The observed effects, regarding the possible high exposition of keratinocytes to toxins including MCs, are severe and may cause diverse health problems.
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