MTOC translocation modulates IS formation and controls sustained T cell signaling

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Abstract

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 ζ 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. © 2008 Martín-Cófreces et al.

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Martín-Cófreces, N. B., Robles-Valero, J., Cabrero, J. R., Mittelbrunn, M., Gordón-Alonso, M., Sung, C. H., … Sánchez-Madrid, F. (2008). MTOC translocation modulates IS formation and controls sustained T cell signaling. Journal of Cell Biology, 182(5), 951–962. https://doi.org/10.1083/jcb.200801014

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