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


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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    • "Eukaryotic cells construct and maintain multiple actin filament networks with different functions: cortical networks that provide mechanical rigidity; lamellipodial networks that drive plasma membrane protrusion; stress fibers that contribute to adhesion; and a contractile ring that divides one cell into two (Michelot and Drubin, 2011). How are these diverse networks, each with a different architecture and a different set of accessory factors, constructed from the same basic building material: the same actin filaments? "
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    ABSTRACT: Most eukaryotic cells express multiple isoforms of the actin-binding protein tropomyosin that help construct a variety of cytoskeletal networks. Only one non-muscle tropomyosin (Tm1A) has previously been described in Drosophila, but developmental defects caused by insertion of P-elements near tropomyosin genes imply the existence of additional, non-muscle isoforms. Using biochemical and molecular genetic approaches, we identified three tropomyosins expressed in Drosophila S2 cells: Tm1A, Tm1J, and Tm2A. The Tm1A isoform localizes to the cell cortex, lamellar actin networks, and the cleavage furrow of dividing cells- always together with myosin-II. Isoforms Tm1J and Tm2A colocalize around the Golgi apparatus with the formin-family protein Diaphanous and loss of either isoform perturbs cell cycle progression. During mitosis, Tm1J localizes to the mitotic spindle where it promotes chromosome segregation. Using chimeras, we identified the determinants of tropomyosin localization near the C-terminus. This work: (i) identifies and characterizes previously unknown non-muscle tropomyosins in Drosophila; (ii) reveals a function for tropomyosin in the mitotic spindle; and (iii) uncovers sequence elements that specify isoform-specific localizations and functions of tropomyosin. © 2015 by The American Society for Cell Biology.
    Molecular biology of the cell 05/2015; 26(13). DOI:10.1091/mbc.E14-12-1619 · 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.
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