The role of ADAP in T cell MTOC polarization

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Combs, Jeffrey Howard

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Binding of T cells to antigen-presenting cells (APCs) leads to the formation of the immunological synapse, translocation of the microtubule-organizing center (MTOC) to the synapse, and focused secretion of effector molecules. Translocation of the MTOC towards the synapse is essential for guiding the microtubule-dependent movement of secretory granules to the secretory zone at the synapse. Although MTOC translocation is essential for T cell effector function, the mechanism of MTOC polarization is still unknown. Here, data are presented that provide insight into the mechanisms of this event. It is shown that upon activation, ADAP forms a ring at the synapse that marks the site where microtubules interact with the cortex. The ADAP ring colocalizes with dynein and the dynein binding proteins β-catenin and PLAC-24. In Jurkat T cells, when ADAP expression is reduced by antisense morpholino oligonucleotides, MTOC translocation is blocked and dynein fails to localize at the synapse. These results suggest the involvement of ADAP in a mechanism that links signaling through the TCR to translocation of the MTOC.