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Diacylglycerol kinase α establishes T cell polarity by shaping diacylglycerol accumulation at the immunological synapse.
- Source :
-
Science signaling [Sci Signal] 2014 Aug 26; Vol. 7 (340), pp. ra82. Date of Electronic Publication: 2014 Aug 26. - Publication Year :
- 2014
-
Abstract
- 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 α (DGK-α), which catalyzes the conversion of DAG to phosphatidic acid, determined T cell polarity by limiting the diffusion of DAG. DGK-α-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-ζ did not display polarization defects. We also found that DGK-α 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-α, which suggests a link between DAG and phosphatidylinositol signaling during T cell activation. These results reveal a previously unappreciated function of DGK-α and provide insight into the mechanisms that determine lymphocyte polarity.<br /> (Copyright © 2014, American Association for the Advancement of Science.)
- Subjects :
- Animals
Diacylglycerol Kinase genetics
Diacylglycerol Kinase immunology
Enzyme-Linked Immunosorbent Assay
Image Processing, Computer-Assisted
Mice
Mice, Transgenic
Phosphatidylinositol 3-Kinases metabolism
Single-Cell Analysis
Statistics, Nonparametric
CD4-Positive T-Lymphocytes cytology
Cell Polarity immunology
Diacylglycerol Kinase metabolism
Diglycerides metabolism
Immunological Synapses metabolism
Microtubule-Organizing Center metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1937-9145
- Volume :
- 7
- Issue :
- 340
- Database :
- MEDLINE
- Journal :
- Science signaling
- Publication Type :
- Academic Journal
- Accession number :
- 25161317
- Full Text :
- https://doi.org/10.1126/scisignal.2005287