title: Distinct Roles of Cytoskeletal Components in Immunological Synapse Formation and Directed Secretion.
abstract: A hallmark of CD4(+) T cell activation and immunological synapse (IS) formation is the migration of the microtubule organization center and associated organelles toward the APCs. In this study, we found that when murine CD4(+) T cells were treated with a microtubule-destabilizing agent (vinblastine) after the formation of IS, the microtubule organization center dispersed and all of the major cellular organelles moved away from the IS. Cytokines were no longer directed toward the synapse but were randomly secreted in quantities similar to those seen in synaptic secretion. However, if the actin cytoskeleton was disrupted at the same time with cytochalasin D, the organelles did not shift away from the IS. These findings suggest that there is a complex interplay between the microtubules and actin cytoskeleton, where microtubules are important for directing particular cytokines into the synapse, but they are not involved in the amount of cytokines that are produced for at least 1 h after IS formation. In addition, we found that they play a critical role in mobilizing organelles to reorient toward the synapse during T cell activation and in stabilizing organelles against the force that is generated through actin polymerization so that they move toward the APCs. These findings show that there is a complex interplay between these major cytoskeletal components during synapse formation and maintenance.
authors.affiliation: Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305; and Department of Molecular Endocrinology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Ueda
authors.affiliation: Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305; and.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305; and.
authors.forename: Jianming
authors.initials: J
authors.lastname: Xie
authors.affiliation: Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305; and mmdavis@stanford.edu.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D016764:Cell Polarity / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D054992:Immunological Synapses / Q000502:physiology*; D051379:Mice; D008870:Microtubules / Q000502:physiology*; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D014747:Vinblastine / Q000494:pharmacology; D020691:rab GTP-Binding Proteins / Q000032:analysis
chemical_list: D016207:Cytokines; D014747:Vinblastine; D020691:rab GTP-Binding Proteins