期刊
JOURNAL OF CELL BIOLOGY
卷 182, 期 5, 页码 951-962出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200801014
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资金
- Instituto de Salud Carlos III
- Ministerio de Sanidad y Consumo, Spain [RD06/0021/2006]
- Ministerio de Educacion y Ciencia of Spain [BFU200508435/BMC]
- Formacion Profesorado Universitario
- Juan March Foundation (Ayuda a la Investigacion Basica 2002)
- Comunidad de Madrid [INSINET0159/2006]
T he 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.
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