title: HTLV-1-Tax and ICAM-1 act on T-cell signal pathways to polarize the microtubule-organizing center at the virological synapse.
abstract: Human T-lymphotropic virus type 1 (HTLV-1) spreads directly between lymphocytes and other cells via a specialized cell-cell contact, termed the virological synapse. The formation of the virological synapse is accompanied by the orientation of the microtubule-organizing center (MTOC) in the infected T cell toward the cell contact region with the noninfected target cell. We previously demonstrated that the combination of intracellular Tax protein expression and the stimulation of the intercellular adhesion molecule-1 (ICAM-1) on the cell surface is sufficient to trigger MTOC polarization in the HTLV-1-infected T cell. However, the mechanism by which Tax and ICAM-1 cause the MTOC polarization is not fully understood. Here we show that the presence of Tax at the MTOC region and its ability to stimulate cyclic AMP-binding protein-dependent pathways are both required for MTOC polarization in the HTLV-1-infected T cell at the virological synapse. Furthermore, we show that the MTOC polarization induced by ICAM-1 engagement depends on activation of the Ras-MEK-ERK signaling pathway. Our findings indicate that efficient MTOC polarization at the virological synapse requires Tax-mediated stimulation of T-cell activation pathways in synergy with ICAM-1 cross-linking. The results also reveal differences in the signaling pathways used to trigger MTOC polarization between the immunologic synapse and the virological synapse.
authors.affiliation: Department of Immunology, Wright-Fleming Institute, Imperial College, Norfolk Pl, London W2 1PG London, United Kingdom.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Nejmeddine
authors.forename: Veera S
authors.initials: VS
authors.lastname: Negi
authors.forename: Sohini
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kim
authors.initials: K
authors.lastname: Orth
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
mesh_terms: D016764:Cell Polarity / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D016356:Gene Products, tax / Q000235:genetics / Q000502:physiology*; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D019169:Jurkat Cells / Q000821:virology; D008561:Membrane Fusion / Q000502:physiology; D022101:Microtubule-Organizing Center / Q000502:physiology / Q000648:ultrastructure*; D020125:Mutation, Missense; D015739:Nocodazole / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology / Q000648:ultrastructure / Q000821:virology*; D050257:Tubulin Modulators / Q000494:pharmacology; D054875:Ubiquitination; D053586:Virus Internalization
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D016356:Gene Products, tax; D047428:Protein Kinase Inhibitors; D050257:Tubulin Modulators; C514970:tax protein, Human T-lymphotrophic virus 1; D018799:Intercellular Adhesion Molecule-1; D003571:Cytochalasin B; D003513:Cycloheximide; D015739:Nocodazole