Building Distinct Actin Filament Networks Review in a Common Cytoplasm

Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA.
Current biology: CB (Impact Factor: 9.57). 07/2011; 21(14):R560-9. DOI: 10.1016/j.cub.2011.06.019
Source: PubMed

ABSTRACT Eukaryotic cells generate a diversity of actin filament networks in a common cytoplasm to optimally perform functions such as cell motility, cell adhesion, endocytosis and cytokinesis. Each of these networks maintains precise mechanical and dynamic properties by autonomously controlling the composition of its interacting proteins and spatial organization of its actin filaments. In this review, we discuss the chemical and physical mechanisms that target distinct sets of actin-binding proteins to distinct actin filament populations after nucleation, resulting in the assembly of actin filament networks that are optimized for specific functions.

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Available from: David G Drubin, Jan 09, 2014
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    • "The weakness with this view of the role of the actin cytoskeleton is the intrinsic assumption that the actin filaments as visualized by phalloidin staining or fractionated by Triton X-100 solubility are compositionally generic. Instead, it has become increasingly clear that this is not true (Michelot and Drubin, 2011). The two cytoskeletal actin isoforms are spatially segregated and functionally distinct (Schevzov et al., 1992; Dugina et al., 2009; Bunnell and Ervasti, 2011). "
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    ABSTRACT: ERK regulated cell proliferation requires multiple phosphorylation events catalysed first by MEK and then Casein Kinase 2 (CK2) followed by interaction with importin7 and subsequent nuclear translocation of pERK. We report that genetic manipulation of a core component of the actin filaments of cancer cells, the tropomyosin Tm5NM1, regulates the proliferation of normal cells both in vitro and in vivo. Mouse embryo fibroblasts (MEFs) lacking Tm5NM1, which have reduced proliferative capacity, are insensitive to inhibition of ERK by peptide and small molecule inhibitors indicating that ERK is unable to regulate proliferation of these knockout (KO) cells. Treatment of wild type MEFs with a CK2 inhibitor to block phosphorylation of the nuclear translocation signal in pERK resulted in greatly decreased cell proliferation and a significant reduction in the nuclear translocation of pERK. In contrast, Tm5NM1 KO MEFs which show reduced nuclear translocation of pERK were unaffected by inhibition of CK2. This suggested that it is nuclear translocation of CK2-phosphorylated pERK which regulates cell proliferation and this capacity is absent in Tm5NM1 KO cells. Proximity ligation assays confirmed a growth factor-stimulated interaction of pERK with Tm5NM1 and that the interaction of pERK with importin7 is greatly reduced in the Tm5NM1 KO cells. © 2015 by The American Society for Cell Biology.
    Molecular biology of the cell 05/2015; 26(13). DOI:10.1091/mbc.E14-10-1453 · 4.47 Impact Factor
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    • "Cell migration is a fundamental cellular process that is important for many physiological functions including embryogenesis, immune response, and tissue repair. It is a coordinated procedure depending on the dynamic actin cytoskeleton reorganization via the formation of specialized cellular structures controlled by actinbinding proteins [1] [2]. Whereas cell migration is important for normal cellular functions, it can be deregulated in cancer cells and contribute to their invasive behaviors. "
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    ABSTRACT: TRIOBP isoforms 4 and 5 (TRIOBP-4/-5) is an actin-bundling protein associated with hearing loss. Here, we showed that TRIOBP-4/-5 was up-regulated in human pancreatic carcinoma cells. Knockdown of TRIOBP-4/-5 led to a loss of filopodia and a decrease in cell motility. Confocal microscopy showed that re-expression of GFP-TRIOBP-4 or -5 restored the filopodial formation in TRIOBP-4/-5-deficient PANC-1 cells. Finally, TRIOBP-4/-5 was shown to be overexpressed in human pancreatic cancer tissues. These results demonstrate a novel role of TRIOBP-4/-5 that promotes the motility of pancreatic cancer cells via regulating actin cytoskeleton reorganization in the filopodia of the cells.
    Cancer Letters 08/2014; 356(2). DOI:10.1016/j.canlet.2014.08.005 · 5.62 Impact Factor
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    • "So what are the attractions of using yeast for studying actin organisation? Well, as eluded to previously the actin cytoskeleton share the same regulatory mechanisms and functions in yeast and mammals, and homologues of the majority of human actin binding proteins (ABPs) responsible for regulating actin dynamics are found in yeasts (Mishra et al. 2014; Michelot and Drubin 2011; Kovar et al. 2010). The yeast contain the basic actomyosin toolbox making them an excellent system to study global regulation and function of this cytoskeleton. "
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    ABSTRACT: This year marks the 30th anniversary of the first description of the cellular distribution of actin within a yeast cell. Since then advances in both molecular genetics and imaging technologies have ensured research within these simple model organisms has blazed a trail in the field of actomyosin research. Many yeast proteins and their functions are functionally conserved in human cells. This, combined with experimental speed, minimal cost and ease of use make the yeasts extremely attractive model organisms for researching diverse cellular processes, including those involving actomyosin. In this chapter, current state-of-the-art fluorescence methodologies being applied to yeast actomyosin research, together with an honest appraisal of their limitations, such as the pitfalls that should be considered when fluorescently labelling proteins interacting within a dynamic cytoskeleton, will be discussed. Papers describing the established techniques developed for yeast localisation studies will be highlighted. This will provide the reader with an informed overview of the arsenal of imaging techniques available to the yeast actomyosin researcher and encourage them to consider novel ways these simple unicellular eukaryotes could be used to address their own research questions.
    EXS 08/2014; 105:277-98. DOI:10.1007/978-3-0348-0856-9_13
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