title: Phosphatidylinositol 5-phosphate regulates invasion through binding and activation of Tiam1.
abstract: PtdIns5P is a lipid messenger acting as a stress-response mediator in the nucleus, and known to maintain cell activation through traffic alterations upon bacterial infection. Here, we show that PtdIns5P regulates actin dynamics and invasion via recruitment and activation of the exchange factor Tiam1 and Rac1. Restricted Rac1 activation results from the binding of Tiam1 DH-PH domains to PtdIns5P. Using an assay that mimics Rac1 membrane anchoring by using Rac1-His and liposomes containing Ni(2+)-NTA modified lipids, we demonstrate that intrinsic Tiam1 DH-PH activity increases when Rac1 is anchored in a PtdIns5P-enriched environment. This pathway appears to be general since it is valid in different pathophysiological models: receptor tyrosine kinase activation, bacterial phosphatase IpgD expression and the invasive NPM-ALK(+) lymphomas. The discovery that PtdIns5P could be a keystone of GTPases and cytoskeleton spatiotemporal regulation opens important research avenues towards unravelling new strategies counteracting cell invasion.
authors.affiliation: INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 31432 Toulouse, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Viaud
authors.affiliation: INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 31432 Toulouse, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lagarrigue
authors.affiliation: INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 31432 Toulouse, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Ramel
authors.affiliation: INSERM, UMR1043, Plateau Technique D'imagerie Cellulaire, Centre de Physiopathologie de Toulouse Purpan, 31024 Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Allart
authors.affiliation: INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 31432 Toulouse, France.
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Chicanne
authors.affiliation: INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 31432 Toulouse, France.
authors.forename: Laurie
authors.initials: L
authors.lastname: Ceccato
authors.affiliation: INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 31432 Toulouse, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Courilleau
authors.affiliation: INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 31432 Toulouse, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Xuereb
authors.affiliation: Institute of Biochemistry and Genetics, University of Basel, Basel 4058, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Pertz
authors.affiliation: 1] INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 31432 Toulouse, France [2] CHU de Toulouse, Laboratoire d'Hématologie, 31059 Toulouse, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Payrastre
authors.affiliation: INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 31432 Toulouse, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Gaits-Iacovoni
mesh_terms: D000199:Actins / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D012763:Shigella flexneri / Q000472:pathogenicity; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D020662:Guanine Nucleotide Exchange Factors; D018129:Phosphatidylinositol Phosphates; C107953:RAC1 protein, human; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; C113567:phosphatidylinositol 5-phosphate; D016220:Fibroblast Growth Factor 1; C425774:IpgD protein, Shigella flexneri; D010744:Phosphoric Monoester Hydrolases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein