Martin-Cofreces, Noa B.Robles-Valero, JavierCabrero, J RománMittelbrunn, MariaGordón-Alonso, MónicaSung, Ching-HwaAlarcón, BalbinoVázquez, JesúsSanchez-Madrid, Francisco2019-02-052019-02-052008-09-08J Cell Biol. 2008; 182(5):951-620021-9525http://hdl.handle.net/20.500.12105/7121The translocation of the microtubule-organizing center (MTOC) toward the nascent immune synapse (IS) is an early step in lymphocyte activation initiated by T cell receptor (TCR) signaling. The molecular mechanisms that control the physical movement of the lymphocyte MTOC remain largely unknown. We have studied the role of the dynein-dynactin complex, a microtubule-based molecular motor, in the process of T cell activation during T cell antigen-presenting cell cognate immune interactions. Impairment of dynein-dynactin complex activity, either by overexpressing the p50-dynamitin component of dynactin to disrupt the complex or by knocking down dynein heavy chain expression to prevent its formation, inhibited MTOC translocation after TCR antigen priming. This resulted in a strong reduction in the phosphorylation of molecules such as zeta chain-associated protein kinase 70 (ZAP70), linker of activated T cells (LAT), and Vav1; prevented the supply of molecules to the IS from intracellular pools, resulting in a disorganized and dysfunctional IS architecture; and impaired interleukin-2 production. Together, these data reveal MTOC translocation as an important mechanism underlying IS formation and sustained T cell signaling.engVoRhttp://creativecommons.org/licenses/by-nc-sa/4.0/Adaptor Proteins, Signal TransducingAntigen-Presenting CellsBiological TransportCD3 ComplexCell LineDynactin ComplexDyneinsGreen Fluorescent ProteinsHumansInterleukin-2Jurkat CellsLymphocyte ActivationLymphocyte Function-Associated Antigen-1Membrane ProteinsMicrotubule-Associated ProteinsMicrotubule-Organizing CenterPhosphorylationProtein SubunitsRNA InterferenceReceptors, Antigen, T-CellSignal TransductionT-LymphocytesAtribución-NoComercial-CompartirIgual 4.0 Internacional187793731825951-6210.1083/jcb.2008010141540-8140The Journal of cell biologyopen access