title: Dynein-driven transport of T cell receptor microclusters regulates immune synapse formation and T cell activation.
abstract: When T cells recognize a peptide-major histocompatibility complex on antigen-presenting cells (APCs), T cell receptor microclusters (TCR-MCs) are generated and move to the center of the T cell-APC interface to form the central supramolecular activation cluster (cSMAC). cSMAC formation depends on stimulation strength and regulates T cell activation. We demonstrate that the dynein motor complex colocalized and coimmunoprecipitated with the TCR complex and that TCR-MCs moved along microtubules (MTs) toward the center of the immune synapse in a dynein-dependent manner to form cSMAC. MTs are located in close proximity to the plasma membrane at the activation site. TCR-MC velocity and cSMAC formation were impaired by dynein or MT inhibitors or by ablation of dynein expression. T cells with impaired cSMAC formation exhibited enhanced cellular activation including protein phosphorylation and interleukin-2 production. These results indicate that cSMAC formation by TCR-MC movement depends on dynein and MTs, and the movement regulates T cell activation.
authors.affiliation: Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hashimoto-Tane
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yokosuka
authors.forename: Kumiko
authors.initials: K
authors.lastname: Sakata-Sogawa
authors.forename: Machie
authors.initials: M
authors.lastname: Sakuma
authors.forename: Chitose
authors.initials: C
authors.lastname: Ishihara
authors.forename: Makio
authors.initials: M
authors.lastname: Tokunaga
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D004398:Dyneins / Q000276:immunology*; D054992:Immunological Synapses / Q000276:immunology* / Q000648:ultrastructure; D008213:Lymphocyte Activation; D051379:Mice; D008854:Microscopy, Electron; D011485:Protein Binding; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D011948:Receptors, Antigen, T-Cell; D004398:Dyneins