title: Phosphatidylinositol 4-Phosphate 5-Kinase β Controls Recruitment of Lipid Rafts into the Immunological Synapse.
abstract: Phosphatidylinositol 4,5-biphosphate (PIP2) is critical for T lymphocyte activation serving as a substrate for the generation of second messengers and the remodeling of actin cytoskeleton necessary for the clustering of lipid rafts, TCR, and costimulatory receptors toward the T:APC interface. Spatiotemporal analysis of PIP2 synthesis in T lymphocytes suggested that distinct isoforms of the main PIP2-generating enzyme, phosphatidylinositol 4-phosphate 5-kinase (PIP5K), play a differential role on the basis of their distinct localization. In this study, we analyze the contribution of PIP5Kβ to T cell activation and show that CD28 induces the recruitment of PIP5Kβ to the immunological synapse, where it regulates filamin A and lipid raft accumulation, as well as T cell activation, in a nonredundant manner. Finally, we found that Vav1 and the C-terminal 83 aa of PIP5Kβ are pivotal for the PIP5Kβ regulatory functions in response to CD28 stimulation.
authors.affiliation: Humanitas University, Rozzano, Milan 20089, Italy; Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Rozzano, Milan 20089, Italy;
authors.forename: Marinos
authors.identifier: http://orcid.org/0000-0001-9318-3368
authors.initials: M
authors.lastname: Kallikourdis
authors.affiliation: Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Rozzano, Milan 20089, Italy;
authors.forename: Anna Elisa
authors.initials: AE
authors.lastname: Trovato
authors.affiliation: Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Rozzano, Milan 20089, Italy;
authors.forename: Giuliana
authors.initials: G
authors.lastname: Roselli
authors.affiliation: Pasteur Institute-Cenci Bolognetti Foundation, Department of Biology and Biotechnology Charles Darwin, Sapienza University, 00185 Rome, Italy; and.
authors.forename: Michela
authors.initials: M
authors.lastname: Muscolini
authors.affiliation: Pasteur Institute-Cenci Bolognetti Foundation, Department of Biology and Biotechnology Charles Darwin, Sapienza University, 00185 Rome, Italy; and.
authors.forename: Nicla
authors.initials: N
authors.lastname: Porciello
authors.affiliation: Pasteur Institute-Cenci Bolognetti Foundation, Department of Biology and Biotechnology Charles Darwin, Sapienza University, 00185 Rome, Italy; and loretta.tuosto@uniroma1.it.
authors.forename: Loretta
authors.initials: L
authors.lastname: Tuosto
authors.affiliation: Department of Biomedical Sciences, University of Padua and Venetian Institute of Molecular Medicine, 35131 Padua, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Viola
mesh_terms: D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D054992:Immunological Synapses / Q000276:immunology*; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D021962:Membrane Microdomains / Q000276:immunology*; D018613:Microscopy, Confocal; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000276:immunology* / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D014162:Transfection
chemical_list: D018106:CD28 Antigens; D007527:Isoenzymes; D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase