Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/7121
MTOC translocation modulates IS formation and controls sustained T cell signaling
Martin-Cofreces, Noa B. CNIC | Robles-Valero, Javier | Cabrero, J Román | Mittelbrunn, Maria CNIC | Gordón-Alonso, Mónica | Sung, Ching-Hwa | Alarcón, Balbino | Vázquez, Jesús CNIC | Sanchez-Madrid, Francisco CNIC
J Cell Biol. 2008; 182(5):951-62
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.
Adaptor Proteins, Signal Transducing | Antigen-Presenting Cells | Biological Transport | CD3 Complex | Cell Line | Dynactin Complex | Dyneins | Green Fluorescent Proteins | Humans | Interleukin-2 | Jurkat Cells | Lymphocyte Activation | Lymphocyte Function-Associated Antigen-1 | Membrane Proteins | Microtubule-Associated Proteins | Microtubule-Organizing Center | Phosphorylation | Protein Subunits | RNA Interference | Receptors, Antigen, T-Cell | Signal Transduction | T-Lymphocytes
Files in this item
- MTOCTranslocationModulatesIS_2 ...