Localized diacylglycerol drives the polarization of the  microtubule-organizing center in T cells.
The reorientation of the T cell microtubule-organizing center (MTOC) toward the antigen-presenting cell enables the directional secretion of cytokines and lytic factors. By single-cell photoactivation of the T cell antigen receptor, we show that MTOC polarization is driven by localized accumulation of diacylglycerol (DAG). MTOC reorientation was closely preceded first by production of DAG and then by recruitment of the microtubule motor protein dynein. Blocking DAG production or disrupting the localization of DAG impaired MTOC recruitment. Localized DAG accumulation was also required for cytotoxic T cell-mediated killing. Furthermore, photoactivation of DAG itself was sufficient to induce transient polarization. Our data identify a DAG-dependent pathway that signals through dynein to control microtubule polarity in T cells.
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Emily J
EJ
Quann
Ernesto
E
Merino
Toshiaki
T
Furuta
Morgan
M
Huse
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D016764:Cell Polarity; D002478:Cells, Cultured; D004075:Diglycerides / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism; D051379:Mice; D022101:Microtubule-Organizing Center / Q000378:metabolism*; D051966:Phospholipase C gamma / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000378:metabolism
D004075:Diglycerides; D011948:Receptors, Antigen, T-Cell; D051966:Phospholipase C gamma; D004398:Dyneins