Journal ArticleDOI
Actin-based motility of vaccinia virus mimics receptor tyrosine kinase signalling.
Friedrich Frischknecht,Violaine Moreau,Sabine Röttger,Stefania Gonfloni,Inge Reckmann,Giulio Superti-Furga,Michael Way +6 more
TLDR
It is suggested that vaccinia virus spreads by mimicking the signalling pathways that are normally involved in actin polymerization at the plasma membrane, including Nck and N-WASP.Abstract:
Studies of the actin-based motility of the intracellular pathogens Listeria monocytogenes and Shigella flexneri have provided important insight into the events occurring at the leading edges of motile cells. Like the bacteria Listeria and Shigella, vaccinia virus, a relative of the causative agent of smallpox, uses actin-based motility to spread between cells. In contrast to Listeria or Shigella, the actin-based motility of vaccinia is dependent on an unknown phosphotyrosine protein, but the underlying mechanism remains obscure. Here we show that phosphorylation of tyrosine 112 in the viral protein A36R by Src-family kinases is essential for the actin-based motility of vaccinia. Tyrosine phosphorylation of A36R results in a direct interaction with the adaptor protein Nck and the recruitment of the Ena/VASP family member N-WASP to the site of actin assembly. We also show that Nck and N-WASP are essential for the actin-based motility of vaccinia virus. We suggest that vaccinia virus spreads by mimicking the signalling pathways that are normally involved in actin polymerization at the plasma membrane.read more
Citations
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Journal ArticleDOI
Cellular Motility Driven by Assembly and Disassembly of Actin Filaments
Thomas D. Pollard,Gary G. Borisy +1 more
TL;DR: A core set of proteins including actin, Arp2/3 complex, profilin, capping protein, and ADF/cofilin can reconstitute the process in vitro, and mathematical models of the constituent reactions predict the rate of motion.
Journal ArticleDOI
Listeria pathogenesis and molecular virulence determinants.
José A. Vázquez-Boland,José A. Vázquez-Boland,Michael Kuhn,Patrick Berche,Trinad Chakraborty,Gustavo Domínguez-Bernal,Werner Goebel,Bruno Gonzalez-Zorn,Jürgen Wehland,Jürgen Kreft +9 more
TL;DR: The molecular determinants of Listeria virulence and their mechanism of action are described and the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listersia infection is summarized.
Journal ArticleDOI
Actin Dynamics, Architecture, and Mechanics in Cell Motility
TL;DR: The feedback loop between biochemical and mechanical properties of actin organization at the molecular level in vitro is described and this knowledge is integrated into the current understanding of cellular actin organizations and its physiological roles.
Journal ArticleDOI
The ARP2/3 complex: an actin nucleator comes of age
Erin D. Goley,Matthew D. Welch +1 more
TL;DR: A decade of study has begun to shed light on the molecular mechanisms by which this powerful machine controls the polymerization, organization and recycling of actin-filament networks, both in vitro and in the living cell.
Journal ArticleDOI
The WASP-WAVE protein network: connecting the membrane to the cytoskeleton.
TL;DR: Wiskott–Aldrich syndrome protein (WASP) and WASP-family verprolin-homologous protein (WAVE) family proteins are scaffolds that link upstream signals to the activation of the ARP2/3 complex, leading to a burst of actin polymerization.
References
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Journal ArticleDOI
Discovery of a Novel, Potent, and Src Family-selective Tyrosine Kinase Inhibitor STUDY OF Lck- AND FynT-DEPENDENT T CELL ACTIVATION
Jeffrey Herbert Hanke,Joseph P. Gardner,Robert L. Dow,Paul S. Changelian,William H. Brissette,Weringer Elora Jeanne,Brian A. Pollok,Patricia A. Connelly +7 more
TL;DR: This compound offers a useful new tool for examining the role of the Lck and FynT tyrosine kinases versus ZAP-70 in T cell activation as well as the roles of other Src family kinases in receptor function.
Journal ArticleDOI
The interaction of Arp2/3 complex with actin: Nucleation, high affinity pointed end capping, and formation of branching networks of filaments
TL;DR: It is shown that Arp2/3 complex purified from Acanthamoeba caps the pointed ends of actin filaments with high affinity and increases the critical concentration for polymerization at the pointed end from 0.6 to 1.0 microM.
Journal ArticleDOI
The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly.
Rajat Rohatgi,Le Ma,Hiroaki Miki,Marco Lopez,Tomas Kirchhausen,Tadaomi Takenawa,Marc W. Kirschner +6 more
TL;DR: N-WASP and the Arp2/3 complex comprise a core mechanism that directly connects signal transduction pathways to the stimulation of actin polymerization.
Journal ArticleDOI
Scar1 and the related Wiskott–Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex
TL;DR: The data suggest that WASP-related proteins may regulate the actin cytoskeleton through the Arp2/3 complex.
Journal ArticleDOI
Scar, a WASp-related protein, activates nucleation of actin filaments by the Arp2/3 complex.
Laura M. Machesky,R D Mullins,Henry N. Higgs,Donald A. Kaiser,Laurent Blanchoin,Robin C. May,Margaret E. Hall,Thomas D. Pollard +7 more
TL;DR: Results show that Scar and, likely, related proteins, such as the Cdc42 targets WASp and N-WASp, are endogenous activators of actin polymerization by the Arp2/3 complex.