Article

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: 9.67). 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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    • "Microbial pathogens modulate the host cell actin cytoskeleton to control phagocytosis, adhesion, cell–cell contacts, movement within the cytosol, spreading to neighboring cells, or development of a niche viable for intracellular bacterial replication (Kumar and Valdivia 2008; Carabeo 2011; Haglund and Welch 2011). This is accomplished by effector proteins that hijack the major eukaryotic actin nucleators Arp2/3 complex and formins (Truong et al. 2014), modulate key regulators of actin dynamics (e.g., Rho GTPases) (Hardt et al. 1998; Egile et al. 1999; Stender et al. 2000; Zhou et al. 2001; Patel and Galan 2006; Rottner et al. 2010), or directly polymerize actin (Hayward and Koronakis 1999; Jewett et al. 2006; Liverman et al. 2007; Haglund et al. 2010; Franco et al. 2012). The actin network also plays a fundamental role in the Legionella infection process. "
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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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    • "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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