Preformed reggie/flotillin caps: stable priming platforms for macrodomain assembly in T cells
Preformed reggie/flotillin caps: stable priming platforms for macrodomain assembly in T cells
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DOI：
10.1096/fj.05-4760fje
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发表时间：
2006-02-01
期刊：
影响因子：
4.8
通讯作者：
Stuermer, Claudia A. O.
中科院分区：
文献类型：
--
作者：
Langhorst, Matthias F.;Reuter, Alexander;Stuermer, Claudia A. O.
与抗原呈递细胞接触后的T细胞活化取决于T细胞受体信号传导复合物的调节组装，其涉及围绕接合的T细胞受体的稳定的筏状宏结构域的极化组装。在这里，我们表明，存在于静息T细胞中的预成型雷吉/flotillin帽作为启动平台的宏域组装。预形成的reggie-1/flotillin-2帽是非常稳定的，如通过光漂白后的荧光恢复（FRAP）所示。在T细胞刺激后，信号分子被募集到稳定的reggie/flotillin帽。重要的是，一个trans-negative reggie-1/flotillin-2缺失突变体，干扰组装的预制reggie/ flotillin帽，损害筏极化和宏域形成后T细胞活化。因此，反式负reggie-1突变体的表达导致鸟嘌呤核苷酸交换因子Vav的不正确定位，导致细胞骨架重组的缺陷。因此，预制的雷吉/ flotillin帽是稳定的启动平台，用于组装多蛋白复合物，控制T细胞活化过程中的肌动蛋白重组。
T cell activation after contact with an antigen-presenting cell depends on the regulated assembly of the T cell receptor signaling complex, which involves the polarized assembly of a stable, raft-like macrodomain surrounding engaged T cell receptors. Here we show that the preformed reggie/flotillin caps present in resting T cells act as priming platforms for macrodomain assembly. Preformed reggie-1/flotillin-2 caps are exceptionally stable, as shown by fluorescence recovery after photobleaching (FRAP). Upon T cell stimulation, signaling molecules are recruited to the stable reggie/flotillin caps. Importantly, a trans-negative reggie-1/flotillin-2 deletion mutant, which interferes with assembly of the preformed reggie/ flotillin cap, impairs raft polarization and macrodomain formation after T cell activation. Accordingly, expression of the trans-negative reggie-1 mutant leads to the incorrect positioning of the guanine nucleotide exchange factor Vav, resulting in defects in cytoskeletal reorganization. Thus, the preformed reggie/ flotillin caps are stable priming platforms for the assembly of multiprotein complexes controlling actin reorganization during T cell activation.