Shigella IpaA mediates actin bundling through diffusible vinculin oligomers with activation imprint
Cesar Valencia-Gallardo,
Daniel-Isui Aguilar-Salvador,
Hamed Khakzad,
Benjamin Cocom-Chan,
Charles Bou-Nader,
Christophe Velours,
Yosra Zarrouk,
Christophe Le Clainche,
Christian Malosse,
Diogo Borges Lima,
Nicole Quenech’Du,
Bilal Mazhar,
Sami Essid,
Marc Fontecave,
Atef Asnacios,
Julia Chamot-Rooke,
Lars Malmström,
Guy Tran Van Nhieu
Affiliations
Cesar Valencia-Gallardo
Center for Interdisciplinary Research in Biology (CIRB), Team “Ca2+ Signaling and Microbial Infections,” Collège de France, CNRS UMR7241/INSERM U1050, PSL Research University, 75005 Paris, France
Daniel-Isui Aguilar-Salvador
Center for Interdisciplinary Research in Biology (CIRB), Team “Ca2+ Signaling and Microbial Infections,” Collège de France, CNRS UMR7241/INSERM U1050, PSL Research University, 75005 Paris, France; Laboratoire de biologie et Pharmacie Appliquée (LBPA), CNRS UMR8113/INSERM U1282, Team “Ca2+ Signaling and Microbial Infections,” Ecole Normale Supérieure Paris-Saclay, Université Paris Saclay, 91190 Gif-sur-Yvette, France
Hamed Khakzad
Center for Interdisciplinary Research in Biology (CIRB), Team “Ca2+ Signaling and Microbial Infections,” Collège de France, CNRS UMR7241/INSERM U1050, PSL Research University, 75005 Paris, France; Laboratoire de biologie et Pharmacie Appliquée (LBPA), CNRS UMR8113/INSERM U1282, Team “Ca2+ Signaling and Microbial Infections,” Ecole Normale Supérieure Paris-Saclay, Université Paris Saclay, 91190 Gif-sur-Yvette, France
Benjamin Cocom-Chan
Center for Interdisciplinary Research in Biology (CIRB), Team “Ca2+ Signaling and Microbial Infections,” Collège de France, CNRS UMR7241/INSERM U1050, PSL Research University, 75005 Paris, France; Laboratoire de biologie et Pharmacie Appliquée (LBPA), CNRS UMR8113/INSERM U1282, Team “Ca2+ Signaling and Microbial Infections,” Ecole Normale Supérieure Paris-Saclay, Université Paris Saclay, 91190 Gif-sur-Yvette, France; Institute for Integrative Biology of the Cell (I2BC), CNRS UMR9198/INSERM U1280, Team “Ca2+ Signaling and Microbial Infections,” CEA, Université Paris-Saclay, 91190 Gif-sur-Yvette, France
Charles Bou-Nader
Laboratoire de Chimie des Processus Biologiques, Collège De France, CNRS UMR8229, 75005 Paris, France
Christophe Velours
Fundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS-University of Bordeaux, SFR TransBioMed, 33076 Bordeaux, France
Yosra Zarrouk
Institute for Integrative Biology of the Cell (I2BC), CNRS UMR9198/INSERM U1280, Team “Ca2+ Signaling and Microbial Infections,” CEA, Université Paris-Saclay, 91190 Gif-sur-Yvette, France
Christophe Le Clainche
Institute for Integrative Biology of the Cell (I2BC), CNRS UMR9198, Team “Cytoskeletal Dynamics and Motility”, CEA, Université Paris-Saclay, 91190 Gif-sur-Yvette, France
Christian Malosse
Institut Pasteur, Université Paris Cité, CNRS UAR 2024, Mass Spectrometry for Biology Unit, F-75015 Paris
Diogo Borges Lima
Institut Pasteur, Université Paris Cité, CNRS UAR 2024, Mass Spectrometry for Biology Unit, F-75015 Paris
Nicole Quenech’Du
Center for Interdisciplinary Research in Biology (CIRB), Team “Ca2+ Signaling and Microbial Infections,” Collège de France, CNRS UMR7241/INSERM U1050, PSL Research University, 75005 Paris, France
Bilal Mazhar
Center for Interdisciplinary Research in Biology (CIRB), Team “Ca2+ Signaling and Microbial Infections,” Collège de France, CNRS UMR7241/INSERM U1050, PSL Research University, 75005 Paris, France
Sami Essid
Laboratoire de biologie et Pharmacie Appliquée (LBPA), CNRS UMR8113/INSERM U1282, Team “Ca2+ Signaling and Microbial Infections,” Ecole Normale Supérieure Paris-Saclay, Université Paris Saclay, 91190 Gif-sur-Yvette, France
Marc Fontecave
Laboratoire de Chimie des Processus Biologiques, Collège De France, CNRS UMR8229, 75005 Paris, France
Atef Asnacios
Université Paris Cité, CNRS, Laboratoire Matière et Systèmes Complexes, UMR7057, F-75013 Paris, France
Julia Chamot-Rooke
Institut Pasteur, Université Paris Cité, CNRS UAR 2024, Mass Spectrometry for Biology Unit, F-75015 Paris
Lars Malmström
Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden
Guy Tran Van Nhieu
Center for Interdisciplinary Research in Biology (CIRB), Team “Ca2+ Signaling and Microbial Infections,” Collège de France, CNRS UMR7241/INSERM U1050, PSL Research University, 75005 Paris, France; Laboratoire de biologie et Pharmacie Appliquée (LBPA), CNRS UMR8113/INSERM U1282, Team “Ca2+ Signaling and Microbial Infections,” Ecole Normale Supérieure Paris-Saclay, Université Paris Saclay, 91190 Gif-sur-Yvette, France; Institute for Integrative Biology of the Cell (I2BC), CNRS UMR9198/INSERM U1280, Team “Ca2+ Signaling and Microbial Infections,” CEA, Université Paris-Saclay, 91190 Gif-sur-Yvette, France; Corresponding author
Summary: Upon activation, vinculin reinforces cytoskeletal anchorage during cell adhesion. Activating ligands classically disrupt intramolecular interactions between the vinculin head and tail domains that bind to actin filaments. Here, we show that Shigella IpaA triggers major allosteric changes in the head domain, leading to vinculin homo-oligomerization. Through the cooperative binding of its three vinculin-binding sites (VBSs), IpaA induces a striking reorientation of the D1 and D2 head subdomains associated with vinculin oligomerization. IpaA thus acts as a catalyst producing vinculin clusters that bundle actin at a distance from the activation site and trigger the formation of highly stable adhesions resisting the action of actin relaxing drugs. Unlike canonical activation, vinculin homo-oligomers induced by IpaA appear to keep a persistent imprint of the activated state in addition to their bundling activity, accounting for stable cell adhesion independent of force transduction and relevant to bacterial invasion.
