Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse
Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse
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DOI：
10.1016/j.immuni.2007.01.008
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发表时间：
2007-02-01
期刊：
影响因子：
32.4
通讯作者：
Billadeau, Daniel D.
中科院分区：
文献类型：
--
作者：
Gomez, Timothy S.;Kumar, Karan;Billadeau, Daniel D.
T细胞受体(TCR)介导的细胞骨架重组被认为是肌动蛋白相关蛋白(Arp)2/3复合体依赖的。因此，我们研究了在T细胞激活过程中对Arp2/3和Forin依赖的F-肌动蛋白成核的要求。我们证明，在没有Arp2/3介导的肌动蛋白成核的情况下，受刺激的T细胞不能形成富含F-肌动蛋白的膜椭圆形，而是产生极化的丝状足状结构。此外，微管组织中心(MTOC，或中心体)，它通过未知的机制快速重定向到免疫突触，在没有Arp2/3的情况下极化。相反，肌动蛋白核形成的Forins，透明的-1(DIA1)和类似Forin-1(FMNL1)，不影响TCR刺激的富含F-肌动蛋白的结构，而是显示出独特的中心体共定位和受控的中心体极化模式。细胞毒淋巴细胞中FMNL1或DIA1的缺失可消除细胞介导的杀伤作用。总之，我们的结果确认了T淋巴细胞中Arp2/3复合体不依赖的细胞骨架重组事件，并表明福尔马林是T细胞中心体极性的必要细胞骨架调节因子。
T cell receptor (TCR)-mediated cytoskeletal reorganization is considered to be actin-related protein (Arp) 2/3 complex dependent. We therefore examined the requirement for Arp2/3- and formin-dependent F-actin nucleation during T cell activation. We demonstrated that without Arp2/3-mediated actin nucleation, stimulated T cells could not form an F-actin-rich lamellipod, but instead produced polarized filopodia-like structures. Moreover, the microtubule-organizing center (MTOC, or centrosome), which rapidly reorients to the immunological synapse through an unknown mechanism, polarized in the absence of Arp2/3. Conversely, the actin-nucleating formins, Diaphanous-1 (DIA1) and Formin-like-1 (FMNL1), did not affect TCR-stimulated F-actin-rich structures, but instead displayed unique patterns of centrosome colocalization and controlled TCR-mediated centrosome polarization. Depletion of FMNL1 or DIA1 in cytotoxic lymphocytes abrogated cell-mediated killing. Altogether, our results have identifed Arp2/3 complex-independent cytoskeletal reorganization events in T lymphocytes and indicate that formins are essential cytoskeletal regulators of centrosome polarity in T cells.