Centre for Vascular Research, University of New South Wales, Sydney, Australia.
Nat Immunol. 2011 Jun 5;12(7):655-62. doi: 10.1038/ni.2049.
Engaged T cell antigen receptors (TCRs) initiate signaling through the adaptor protein Lat. In quiescent T cells, Lat is segregated into clusters on the cell surface, which raises the question of how TCR triggering initiates signaling. Using super-resolution fluorescence microscopy, we found that pre-existing Lat domains were neither phosphorylated nor laterally transported to TCR activation sites, which suggested that these clusters do not participate in TCR signaling. Instead, TCR activation resulted in the recruitment and phosphorylation of Lat from subsynaptic vesicles. Studies of Lat mutants confirmed that recruitment preceded and was essential for phosphorylation and that both processes were independent of surface clustering of Lat. Our data suggest that TCR ligation preconditions the membrane for vesicle recruitment and bulk activation of the Lat signaling network.
参与的 T 细胞抗原受体 (TCRs) 通过衔接蛋白 Lat 启动信号转导。在静止的 T 细胞中，Lat 被分隔在细胞表面的簇上，这就提出了一个问题，即 TCR 触发如何启动信号转导。使用超分辨率荧光显微镜，我们发现预先存在的 Lat 结构域既没有磷酸化，也没有横向运输到 TCR 激活位点，这表明这些簇不参与 TCR 信号转导。相反，TCR 的激活导致 Lat 从亚突触小泡中募集和磷酸化。Lat 突变体的研究证实，募集先于磷酸化发生，并且这两个过程都不依赖于 Lat 在表面的聚类。我们的数据表明，TCR 连接预先为囊泡募集和 Lat 信号网络的整体激活做好了膜的准备。
