title: Centrosome repositioning in T cells is biphasic and driven by microtubule end-on capture-shrinkage.
abstract: T cells rapidly reposition their centrosome to the center of the immunological synapse (IS) to drive polarized secretion in the direction of the bound target cell. Using an optical trap for spatial and temporal control over target presentation, we show that centrosome repositioning in Jurkat T cells exhibited kinetically distinct polarization and docking phases and required calcium flux and signaling through both the T cell receptor and integrin to be robust. In "frustrated" conjugates where the centrosome is stuck behind the nucleus, the center of the IS invaginated dramatically to approach the centrosome. Consistently, imaging of microtubules during normal repositioning revealed a microtubule end-on capture-shrinkage mechanism operating at the center of the IS. In agreement with this mechanism, centrosome repositioning was impaired by inhibiting microtubule depolymerization or dynein. We conclude that dynein drives centrosome repositioning in T cells via microtubule end-on capture-shrinkage operating at the center of the IS and not cortical sliding at the IS periphery, as previously thought.
authors: Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute NHLBI, National Institutes of Health, NIH, Bethesda, MD 20892, USA.
authors: Jason
authors: J
authors: Yi
authors: Xufeng
authors: X
authors: Wu
authors: Andrew H
authors: AH
authors: Chung
authors: James K
authors: JK
authors: Chen
authors: Tarun M
authors: TM
authors: Kapoor
authors: John A
authors: JA
authors: Hammer
mesh_terms: D000938:Antigen-Presenting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D018385:Centrosome / Q000187:drug effects / Q000378:metabolism*; D004398:Dyneins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses / Q000187:drug effects / Q000378:metabolism; D019169:Jurkat Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D022101:Microtubule-Organizing Center / Q000187:drug effects / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D052898:Optical Tweezers; D017239:Paclitaxel / Q000494:pharmacology; D058105:Polymerization / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D004398:Dyneins; D017239:Paclitaxel; D015739:Nocodazole; D002118:Calcium
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