title: Direct interaction between exocyst and Wave complexes promotes cell protrusions and motility.
abstract: Coordination between membrane trafficking and actin polymerization is fundamental in cell migration, but a dynamic view of the underlying molecular mechanisms is still missing. The Rac1 GTPase controls actin polymerization at protrusions by interacting with its effector, the Wave regulatory complex (WRC). The exocyst complex, which functions in polarized exocytosis, has been involved in the regulation of cell motility. Here, we show a physical and functional connection between exocyst and WRC. Purified components of exocyst and WRC directly associate in vitro, and interactions interfaces are identified. The exocyst-WRC interaction is confirmed in cells by co-immunoprecipitation and is shown to occur independently of the Arp2/3 complex. Disruption of the exocyst-WRC interaction leads to impaired migration. By using time-lapse microscopy coupled to image correlation analysis, we visualized the trafficking of the WRC towards the front of the cell in nascent protrusions. The exocyst is necessary for WRC recruitment at the leading edge and for resulting cell edge movements. This direct link between the exocyst and WRC provides a new mechanistic insight into the spatio-temporal regulation of cell migration.
authors: Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris 75005, France ART group, Inserm U830, Paris 75005, France.
authors: Marco
authors: M
authors: Biondini
authors: Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris 75005, France ART group, Inserm U830, Paris 75005, France.
authors: Amel
authors: A
authors: Sadou-Dubourgnoux
authors: Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris 75005, France Cell and Tissue Imaging Facility (PICT-IBiSA), CNRS UMR 144, Paris 75005, France.
authors: Perrine
authors: P
authors: Paul-Gilloteaux
authors: Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris 75005, France ART group, Inserm U830, Paris 75005, France.
authors: Giulia
authors: G
authors: Zago
authors: Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris 75005, France ART group, Inserm U830, Paris 75005, France.
authors: Melis D
authors: MD
authors: Arslanhan
authors: Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris 75005, France Cell and Tissue Imaging Facility (PICT-IBiSA), CNRS UMR 144, Paris 75005, France.
authors: François
authors: F
authors: Waharte
authors: Hybrigenics, Paris 75014, France.
authors: Etienne
authors: E
authors: Formstecher
authors: Laboratoire de Microbiologie et Génétique Moléculaire, CNRS UMR 5100, Université Paul Sabatier, Toulouse 31062, France.
authors: Maud
authors: M
authors: Hertzog
authors: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris-Saclay, CEA-Saclay, Gif-sur-Yvette 91191.
authors: Jinchao
authors: J
authors: Yu
authors: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris-Saclay, CEA-Saclay, Gif-sur-Yvette 91191.
authors: Raphael
authors: R
authors: Guerois
authors: Laboratoire de Biochimie Ecole Polytechnique, CNRS UMR7654, Palaiseau Cedex 91128, France.
authors: Alexis
authors: A
authors: Gautreau
authors: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare and Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan 20139, Italy.
authors: Giorgio
authors: G
authors: Scita
authors: Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris 75005, France ART group, Inserm U830, Paris 75005, France.
authors: Jacques
authors: J
authors: Camonis
authors: Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris 75005, France ART group, Inserm U830, Paris 75005, France maria-carla.parrini@curie.fr.
authors: Maria Carla
authors: 0000-0002-7082-9792
authors: MC
authors: Parrini
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D002465:Cell Movement; D022081:Cell Surface Extensions / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*
chemical_list: C513733:ABI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; D033921:Vesicular Transport Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family
keywords: Exocyst; Motility; Ral; Wave