Recruitment of dynein to the Jurkat immunological synapse.
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.
Combs
Jeffrey
J
Department of Molecular Cell and Developmental Biology, University of Texas, 1 University Station, MC C0930, Austin, TX 78712, USA.
Kim
Soo Jin
SJ
Tan
Sarah
S
Ligon
Lee A
LA
Holzbaur
Erika L F
EL
Kuhn
Jeffrey
J
Poenie
Martin
M
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D004398:Dyneins / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D022101:Microtubule-Organizing Center / Q000187:drug effects / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C106957:FYB1 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D016376:Oligonucleotides, Antisense; D051176:beta Catenin; D004398:Dyneins