Esteban Veiga

Publications (23) View all

• Source

  Available from: María Mittelbrunn

  Article: Endosomal clathrin drives actin accumulation at the immunological synapse.

  Carmen Calabia-Linares, Javier Robles-Valero, Hortensia de la Fuente, Manuel Perez-Martinez, Noa Martín-Cofreces, Manuel Alfonso-Pérez, Cristina Gutierrez-Vázquez, María Mittelbrunn, Sales Ibiza, Francisco R Urbano-Olmos, Covadonga Aguado-Ballano, Carlos Oscar Sánchez-Sorzano, Francisco Sanchez-Madrid, Esteban Veiga
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  ABSTRACT: Antigen-specific cognate interaction of T lymphocytes with antigen-presenting cells (APCs) drives major morphological and functional changes in T cells, including actin rearrangements at the immune synapse (IS) formed at the cell-cell contact area. Here we show, using cell lines as well as primary cells, that clathrin, a protein involved in endocytic processes, drives actin accumulation at the IS. Clathrin is recruited towards the IS with parallel kinetics to that of actin. Knockdown of clathrin prevents accumulation of actin and proteins involved in actin polymerization, such as dynamin-2, the Arp2/3 complex and CD2AP at the IS. The clathrin pool involved in actin accumulation at the IS is linked to multivesicular bodies that polarize to the cell-cell contact zone, but not to plasma membrane or Golgi complex. These data underscore the role of clathrin as a platform for the recruitment of proteins that promote actin polymerization at the interface of T cells and APCs.
  Journal of Cell Science 03/2011; 124(Pt 5):820-30. · 6.11 Impact Factor
• Article: The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse.

  Francesc Baixauli, Noa B Martín-Cófreces, Giulia Morlino, Yolanda R Carrasco, Carmen Calabia-Linares, Esteban Veiga, Juan M Serrador, Francisco Sánchez-Madrid
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  ABSTRACT: During antigen-specific T-cell activation, mitochondria mobilize towards the vicinity of the immune synapse. We show here that the mitochondrial fission factor dynamin-related protein 1 (Drp1) docks at mitochondria, regulating their positioning and activity near the actin-rich ring of the peripheral supramolecular activation cluster (pSMAC) of the immune synapse. Mitochondrial redistribution in response to T-cell receptor engagement was abolished by Drp1 silencing, expression of the phosphomimetic mutant Drp1S637D and the Drp1-specific inhibitor mdivi-1. Moreover, Drp1 knockdown enhanced mitochondrial depolarization and T-cell receptor signal strength, but decreased myosin phosphorylation, ATP production and T-cell receptor assembly at the central supramolecular activation cluster (cSMAC). Our results indicate that Drp1-dependent mitochondrial positioning and activity controls T-cell activation by fuelling central supramolecular activation cluster assembly at the immune synapse.
  The EMBO Journal 02/2011; 30(7):1238-50. · 9.20 Impact Factor
• Article: Escherichia coli producing CNF1 toxin hijacks Tollip to trigger Rac1-dependent cell invasion.

  Orane Visvikis, Laurent Boyer, Stéphanie Torrino, Anne Doye, Marc Lemonnier, Patrick Lorès, Monica Rolando, Gilles Flatau, Amel Mettouchi, Daniel Bouvard, Esteban Veiga, Gérard Gacon, Pascale Cossart, Emmanuel Lemichez
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  ABSTRACT: Rho GTPases, which are master regulators of both the actin cytoskeleton and membrane trafficking, are often hijacked by pathogens to enable their invasion of host cells. Here we report that the cytotoxic necrotizing factor-1 (CNF1) toxin of uropathogenic Escherichia coli (UPEC) promotes Rac1-dependent entry of bacteria into host cells. Our screen for proteins involved in Rac1-dependent UPEC entry identifies the Toll-interacting protein (Tollip) as a new interacting protein of Rac1 and its ubiquitinated forms. We show that knockdown of Tollip reduces CNF1-induced Rac1-dependent UPEC entry. Tollip depletion also reduces the Rac1-dependent entry of Listeria monocytogenes expressing InlB invasion protein. Moreover, knockdown of Tollip, Tom1 and clathrin, decreases CNF1 and Rac1-dependent internalization of UPEC. Finally, we show that Tollip, Tom1 and clathrin associate with Rac1 and localize at the site of bacterial entry. Collectively, these findings reveal a new link between Rac1 and Tollip, Tom1 and clathrin membrane trafficking components hijacked by pathogenic bacteria to allow their efficient invasion of host cells.
  Traffic 02/2011; 12(5):579-90. · 4.92 Impact Factor
• Source

  Available from: Laurent Dortet

  Article: CD44-independent activation of the Met signaling pathway by HGF and InlB.

  Laurent Dortet, Esteban Veiga, Matteo Bonazzi, Pascale Cossart
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  ABSTRACT: Listeria monocytogenes is a facultative intracellular Gram-positive bacterium responsible for listeriosis. It is able to invade, survive and replicate in phagocytic and non-phagocytic cells. The L. monocytogenes surface protein InlB interacts with c-Met, the hepatocyte growth factor (HGF) receptor, inducing bacterial internalization in numerous non-phagocytic cells. As InlB and HGF are known to trigger similar signaling pathways upon c-Met activation, we investigated the role of CD44, and more specifically its isoform CD44v6, in bacterial internalization in non-phagocytic cells. Indeed, CD44, the hyaluronic acid transmembrane receptor, and more specifically its isoform CD44v6 have been reported as necessary for the activation of c-Met upon the interaction with either the endogenous ligand HGF or the L. monocytogenes surface protein InlB. Our results demonstrate that, in the cell lines that we used, CD44 receptors play no role in the activation of c-Met, neither during L. monocytogenes entry, nor upon HGF activation. Furthermore, none of the CD44 isoforms was recruited at the L. monocytogenes entry site, and depletion by siRNA of total CD44 or of CD44v6 isoform did not reduce bacterial infections. Conversely, the overexpression of CD44 or CD44v6 had no significant effect on L. monocytogenes internalization. Together our results reveal that the activation of c-Met can be largely CD44-independent.
  Microbes and Infection 11/2010; 12(12-13):919-27. · 3.10 Impact Factor
• Article: Role for CD2AP and other endocytosis-associated proteins in enteropathogenic Escherichia coli pedestal formation.

  Julian A Guttman, Ann E Lin, Esteban Veiga, Pascale Cossart, B Brett Finlay
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  ABSTRACT: Enteropathogenic Escherichia coli (EPEC) strains are extracellular pathogens that generate actin-rich structures (pedestals) beneath the adherent bacteria as part of their virulence strategy. Pedestals are hallmarks of EPEC infections, and their efficient formation in vitro routinely requires phosphorylation of the EPEC effector protein Tir at tyrosine 474 (Y474). This phosphorylation results in the recruitment and direct attachment of the host adaptor protein Nck to Tir at Y474, which is utilized for actin nucleation through a downstream N-WASP-Arp2/3-based mechanism. Recently, the endocytic protein clathrin was demonstrated to be involved in EPEC pedestal formation. Here we examine the organization of clathrin in pedestals and report that CD2AP, an endocytosis-associated and cortactin-binding protein, is a novel and important component of EPEC pedestal formation that also utilizes Y474 phosphorylation of EPEC Tir. We also demonstrate the successive recruitment of Nck and then clathrin prior to actin polymerization at pedestals during the Nck-dependent pathway of pedestal formation. This study further demonstrates that endocytic proteins are key components of EPEC pedestals and suggests a novel endocytosis subversion strategy employed by these extracellular bacteria.
  Infection and immunity 08/2010; 78(8):3316-22. · 4.21 Impact Factor