title: Rac1-Rab11-FIP3 regulatory hub coordinates vesicle traffic with actin remodeling and T-cell activation.
abstract: The immunological synapse generation and function is the result of a T-cell polarization process that depends on the orchestrated action of the actin and microtubule cytoskeleton and of intracellular vesicle traffic. However, how these events are coordinated is ill defined. Since Rab and Rho families of GTPases control intracellular vesicle traffic and cytoskeleton reorganization, respectively, we investigated their possible interplay. We show here that a significant fraction of Rac1 is associated with Rab11-positive recycling endosomes. Moreover, the Rab11 effector FIP3 controls Rac1 intracellular localization and Rac1 targeting to the immunological synapse. FIP3 regulates, in a Rac1-dependent manner, key morphological events, like T-cell spreading and synapse symmetry. Finally, Rab11-/FIP3-mediated regulation is necessary for T-cell activation leading to cytokine production. Therefore, Rac1 endosomal traffic is key to regulate T-cell activation.
authors.affiliation: Lymphocyte Cell Biology Unit, Department of Immunology, Institut Pasteur, Paris, France CNRS URA 1961, Paris, France INSERM U1221, Paris, France jerome.bouchet@inserm.fr andres.alcover@pasteur.fr.
authors.forename: Jérôme
authors.identifier: 0000-0002-6611-4380
authors.initials: J
authors.lastname: Bouchet
authors.affiliation: Lymphocyte Cell Biology Unit, Department of Immunology, Institut Pasteur, Paris, France CNRS URA 1961, Paris, France INSERM U1221, Paris, France.
authors.forename: Iratxe
authors.initials: I
authors.lastname: Del Río-Iñiguez
authors.affiliation: Lymphocyte Cell Biology Unit, Department of Immunology, Institut Pasteur, Paris, France CNRS URA 1961, Paris, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Lasserre
authors.affiliation: Lymphocyte Cell Biology Unit, Department of Immunology, Institut Pasteur, Paris, France CNRS URA 1961, Paris, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Agüera-Gonzalez
authors.affiliation: Lymphocyte Cell Biology Unit, Department of Immunology, Institut Pasteur, Paris, France CNRS URA 1961, Paris, France INSERM U1221, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Cuche
authors.affiliation: Institut Pasteur Citech-Imagopole, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Danckaert
authors.affiliation: Molecular Cell Biology Laboratory, Biosciences Institute, School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland.
authors.forename: Mary W
authors.initials: MW
authors.lastname: McCaffrey
authors.affiliation: Lymphocyte Cell Biology Unit, Department of Immunology, Institut Pasteur, Paris, France CNRS URA 1961, Paris, France INSERM U1221, Paris, France.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Bartolo
authors.affiliation: Lymphocyte Cell Biology Unit, Department of Immunology, Institut Pasteur, Paris, France CNRS URA 1961, Paris, France INSERM U1221, Paris, France jerome.bouchet@inserm.fr andres.alcover@pasteur.fr.
authors.forename: Andrés
authors.identifier: 0000-0002-9507-3450
authors.initials: A
authors.lastname: Alcover
mesh_terms: D000199:Actins / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D054992:Immunological Synapses / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D034741:RNA, Small Interfering / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D000199:Actins; D051550:I-kappa B Kinase; D007376:Interleukin-2; D034741:RNA, Small Interfering; D020691:rab GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000099193:rab11 GTP-Binding Proteins; C491731:IKBKG protein, human; C508594:IL2 protein, human; C107953:RAC1 protein, human
keywords: Rab11‐FIP3; Rac1; actin cytoskeleton; immunological synapse; intracellular traffic; recycling endosomes