Arp2/3-independent assembly of actin by Vibrio type III effector VopL

Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 11/2007; 104(43):17117-22. DOI: 10.1073/pnas.0703196104
Source: PubMed

ABSTRACT Microbial pathogens use a variety of mechanisms to disrupt the actin cytoskeleton during infection. Vibrio parahaemolyticus (V. para) is a Gram-negative bacterium that causes gastroenteritis, and new pandemic strains are emerging throughout the world. Analysis of the V. para genome revealed a type III secretion system effector, VopL, encoding three Wiskott-Aldrich homology 2 domains that are interspersed with three proline-rich motifs. Infection of HeLa cells with V. para induces the formation of long actin fibers in a VopL-dependent manner. Transfection of VopL promotes the assembly of actin stress fibers. In vitro, recombinant VopL potently induces assembly of actin filaments that grow at their barbed ends, independent of eukaryotic factors. Vibrio VopL is predicted to be a bacterial virulence factor that disrupts actin homeostasis during an enteric infection of the host.

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Available from: Dara L Burdette, Jul 28, 2015
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    • "(Makino et al., 2003), which blocks the MAPKs signaling pathway by inhibiting the start and biological activity of mitogen-activated protein kinase (Trosky et al., 2004), thereby suppressing cell division via a new mechanism. Vop L (VPA1370) contains three Wiskott Aldrich homology 2 (WH2) domains and a C-terminal domain (VCD; Namgoong et al., 2011; Yu et al., 2011), which generally induces the formation of polarized actin fibers and accelerates the gathering of actin filaments by binding to actin monomers (Liverman et al., 2007). Notably, Vop L may provide a favorable microenvironment in which bacteria can replicate, thereby enhancing the uptake and invasion of V. parahaemolyticus. "
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    ABSTRACT: Vibrio parahaemolyticus, a Gram-negative motile bacterium that inhabits marine and estuarine environments throughout the world, is a major food-borne pathogen that causes life-threatening diseases in humans after the consumption of raw or undercooked seafood. The global occurrence of V. parahaemolyticus accentuates the importance of investigating its virulence factors and their effects on the human host. This review describes the virulence factors of V. parahaemolyticus reported to date, including hemolysin, urease, two type III secretion systems and two type VI secretion systems, which both cause both cytotoxicity in cultured cells and enterotoxicity in animal models. We describe various types of detection methods, based on virulence factors, that are used for quantitative detection of V. parahaemolyticus in seafood. We also discuss some useful preventive measures and therapeutic strategies for the diseases mediated by V. parahaemolyticus, which can reduce, to some extent, the damage to humans and aquatic animals attributable to V. parahaemolyticus. This review extends our understanding of the pathogenic mechanisms of V. parahaemolyticus mediated by virulence factors and the diseases it causes in its human host. It should provide new insights for the diagnosis, treatment, and prevention of V. parahaemolyticus infection.
    Frontiers in Microbiology 03/2015; 6:144. DOI:10.3389/fmicb.2015.00144 · 3.94 Impact Factor
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    • "The tandem WH2 array of VopL is a weak actin nucleator on its own; nucleation activity is improved through VopL dimerization, which is mediated by the effector's C-terminal domain (Yu et al., 2011). Cell expression of VopL causes a dramatic actin phenotype characterized by formation of stress fibres that span the whole cell body (Liverman et al., 2007) (Fig. 3). Stress fibres exert tension that allows cell reshaping; this may prove beneficial for bacterial entry or for maintenance of cell structure during bacterial replication. "
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    ABSTRACT: Entry into host cells and intracellular persistence by invasive bacteria are tightly coupled to the ability of the bacterium to disrupt the eukaryotic cytoskeletal machinery. Herein we review the main strategies used by three intracellular pathogens to harness key modulators of the cytoskeleton. Two of these bacteria, namely Listeria monocytogenes and Salmonella enterica serovar Typhimurium, exhibit quite distinct intracellular lifestyles, and therefore, provide a comprehensive panel for the understanding of the intricate bacteria-cytoskeleton interplay during infections. The emerging intracellular pathogen Vibrio parahaemolyticus is depicted as a developing model for the uncovering of novel mechanisms used to hijack the cytoskeleton. This article is protected by copyright. All rights reserved.
    Cellular Microbiology 12/2014; 17(2). DOI:10.1111/cmi.12399 · 4.82 Impact Factor
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    • "Vibrio parahaemolyticus, like many bacterial pathogens, hijacks eukaryotic cytoskeletal processes through injection of effector proteins into host cells (Alto and Orth, 2012; Haglund and Welch, 2011). One of the effector proteins that Vibrio parahaemolyticus injects is the actin nucleation factor VopL. VopL injection causes a substantial reorganization of the host cytoskeleton (Liverman et al., 2007), leading to the formation of characteristic actin stress fibers. VopL has two distinct domains: an N-terminal array of three WH2 motifs and a unique VopL C-terminal domain (VCD). "
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    ABSTRACT: VopL is an effector protein from Vibrio parahaemolyticus that nucleates actin filaments. VopL consists of a VopL C-terminal domain (VCD) and an array of three WASP homology 2 (WH2) motifs. Here, we report the crystal structure of the VCD dimer bound to actin. The VCD organizes three actin monomers in a spatial arrangement close to that found in the canonical actin filament. In this arrangement, WH2 motifs can be modeled into the binding site of each actin without steric clashes. The data suggest a mechanism of nucleation wherein VopL creates filament-like structures, organized by the VCD with monomers delivered by the WH2 array, that can template addition of new subunits. Similarities with Arp2/3 complex and formin proteins suggest that organization of monomers into filament-like structures is a general and central feature of actin nucleation. PAPERFLICK:
    Cell 10/2013; 155(2):423-434. DOI:10.1016/j.cell.2013.09.019 · 33.12 Impact Factor
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