Recruitment of dynein to the Jurkat immunological synapse

被引:152
作者
Combs, Jeffrey
Kim, Soo Jin
Tan, Sarah
Ligon, Lee A.
Holzbaur, Erika L. F.
Kuhn, Jeffrey
Poenie, Martin
机构
[1] Univ Texas, Dept Mol Cell & Dev Biol, Austin, TX 78712 USA
[2] Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA
[3] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA
关键词
microtubules; T cell polarization; beta-catenin; PLAC-24;
D O I
10.1073/pnas.0600914103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Binding of T cells to antigen-presenting cells leads to the formation of the immunological synapse, translocation of the microtubule-organizing center (MTOC) to the synapse, and focused secretion of effector molecules. Here, we show that upon activation of Jurkat cells microtubules project from the MTOC to a ring of the scaffolding protein ADAP, localized at the synapse. Loss of ADAP, but not lymphocyte function-associated antigen 1, leads to a severe defect in MTOC polarization at the immunological synapse. The microtubule motor protein cytoplasmic dynein clusters into a ring at the synapse, colocalizing with the ADAP ring. ADAP coprecipitates with dynein from activated Jurkat cells, and loss of ADAP prevents MTOC translocation and the specific recruitment of dynein to the synapse. These results suggest a mechanism that links signaling through the T cell receptor to translocation of the MTOC, in which the minus end-directed motor cytoplasmic dynein, localized at the synapse through an interaction with ADAP, reels in the MTOC, allowing for directed secretion along the polarized microtubule cytoskeleton.
引用
收藏
页码:14883 / 14888
页数:6
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