| First Author | Chauveau A | Year | 2014 |
| Journal | Sci Signal | Volume | 7 |
| Issue | 340 | Pages | ra82 |
| PubMed ID | 25161317 | Mgi Jnum | J:259454 |
| Mgi Id | MGI:6141342 | Doi | 10.1126/scisignal.2005287 |
| Citation | Chauveau A, et al. (2014) Diacylglycerol kinase alpha establishes T cell polarity by shaping diacylglycerol accumulation at the immunological synapse. Sci Signal 7(340):ra82 |
| abstractText | Polarization of the T cell microtubule-organizing center (MTOC) to the immunological synapse between the T cell and an antigen-presenting cell (APC) maintains the specificity of T cell effector responses by enabling directional secretion toward the APC. The reorientation of the MTOC is guided by a sharp gradient of the second messenger diacylglycerol (DAG), which is centered at the immunological synapse. We used a single-cell photoactivation approach to demonstrate that diacylglycerol kinase alpha (DGK-alpha), which catalyzes the conversion of DAG to phosphatidic acid, determined T cell polarity by limiting the diffusion of DAG. DGK-alpha-deficient T cells exhibited enlarged accumulations of DAG at the immunological synapse, as well as impaired reorientation of the MTOC. In contrast, T cells lacking the related isoform DGK-zeta did not display polarization defects. We also found that DGK-alpha localized preferentially to the periphery of the immunological synapse, suggesting that it constrained the area over which DAG accumulated. Phosphoinositide 3-kinase activity was required for the peripheral localization pattern of DGK-alpha, which suggests a link between DAG and phosphatidylinositol signaling during T cell activation. These results reveal a previously unappreciated function of DGK-alpha and provide insight into the mechanisms that determine lymphocyte polarity. |
