Diacylglycerol kinase α establishes T cell polarity by shaping diacylglycerol accumulation at the immunological synapse.
Diacylglycerol kinase α establishes T cell polarity by shaping diacylglycerol accumulation at the immunological synapse.
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DOI：
10.1126/scisignal.2005287
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发表时间：
2014-08-26
影响因子：
7.3
通讯作者：
Huse M
中科院分区：
文献类型：
--
作者：
Chauveau A;Le Floc'h A;Bantilan NS;Koretzky GA;Huse M
T细胞微管组织中心（MTOC）向免疫突触的极化通过使抗原呈递细胞定向分泌来维持效应器应答的特异性。MTOC重定向由以突触为中心的甘油二酯的急剧梯度引导。在这里，我们使用单细胞光活化方法来证明二酰基甘油激酶-α（DGK-α）通过限制二酰基甘油的扩散来控制T细胞极性。DGK-α缺陷型T细胞表现出突触二酰甘油积聚增加和MTOC重定向受损。相比之下，缺乏相关同种型DGK-T的T细胞不显示极化缺陷。我们还发现DGK-α优先定位于突触的外周，这表明它限制了来自外部的二酰甘油积累的范围。磷酸肌醇3-激酶活性需要这种外周定位模式，在T细胞活化过程中建立了一个有趣的联系甘油二酯和磷脂酰肌醇信号。这些结果揭示了DGK-α以前未被认识的功能，并提供了对淋巴细胞极性机制的深入了解。
Polarization of the T cell microtubule-organizing center (MTOC) to the immunological synapse maintains the specificity of effector responses by enabling directional secretion toward the antigen-presenting cell. MTOC reorientation is guided by a sharp gradient of diacylglycerol that is centered at the synapse. Here, we used a single cell photoactivation approach to demonstrate that diacylglycerol kinase-α (DGK-α) controls T cell polarity by limiting the diffusion of diacylglycerol. DGK-α deficient T cells exhibited enlarged synaptic diacylglycerol accumulations and impaired MTOC reorientation. By 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 synapse, suggesting that it constrains the scope of diacylglycerol accumulation from the outside. Phosphoinositide 3-kinase activity was required for this peripheral localization pattern, establishing an intriguing link between diacylglycerol and phosphatidylinositol signaling during T cell activation. These results reveal a previously unappreciated function of DGK-α and provide insight into the mechanisms of lymphocyte polarity.