2026-06-14T03:30:37Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/71212024-09-27T09:25:45Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Martin-Cofreces, Noa B. author Robles-Valero, Javier author Cabrero, J Román author Mittelbrunn, Maria author Gordón-Alonso, Mónica author Sung, Ching-Hwa author Alarcón, Balbino author Vázquez, Jesús author Sanchez-Madrid, Francisco author 2008-09-08 The 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. J Cell Biol. 2008; 182(5):951-62 10.1083/jcb.200801014 1540-8140 0021-9525 The Journal of cell biology 18779373 http://hdl.handle.net/20.500.12105/7121 MTOC translocation modulates IS formation and controls sustained T cell signaling