Cytoskeletal actin dynamics shape a ramifying actin network underpinning immunological synapse formation.
Cytoskeletal actin dynamics shape a ramifying actin network underpinning immunological synapse formation.
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DOI：
10.1126/sciadv.1603032
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发表时间：
2017-06
期刊：
影响因子：
13.6
通讯作者：
Eggeling C
中科院分区：
文献类型：
--
作者：
Fritzsche M;Fernandes RA;Chang VT;Colin-York H;Clausen MP;Felce JH;Galiani S;Erlenkämper C;Santos AM;Heddleston JM;Pedroza-Pacheco I;Waithe D;de la Serna JB;Lagerholm BC;Liu TL;Chew TL;Betzig E;Davis SJ;Eggeling C
活化的T细胞重组它们的皮质肌动蛋白，在免疫突触下形成分支的运输网络。免疫突触形成过程中T细胞活化，特别是T细胞受体微簇的运输被广泛认为依赖于细胞骨架重塑。然而，在后者的运输过程中参与肌动蛋白的重要细节是失踪。使用一套先进的光学显微镜分析休息和激活的T细胞，我们表明，接触形成与激活表面，这些细胞顺序重新排列其皮质肌动蛋白在整个细胞，创建一个以前未报告的分枝肌动蛋白网络以上的免疫突触。该网络显示了向内生长的运输网络的所有特征及其与T细胞受体重排相关的动力学。这种肌动蛋白重组伴随着纳米级肌动蛋白网络尺寸的增加和两种不同尺寸的丝状肌动蛋白群体的周转时间和细丝长度的动态调整，其中formin介导的长肌动蛋白细丝支持在免疫突触界面处非常平坦和刚性的接触。正如钙释放所强调的那样，免疫突触形成的启动需要与激活表面的接触非常少，并且不需要细胞骨架重排。我们的工作表明，在T细胞中的初始信号启动全球细胞骨架重排整个细胞，包括可能机械支持接触形成在免疫突触接口以及一个中央分支运输网络显然是针对巩固的接触和交付效应器功能的硬化过程。
Activating T cells reorganize their cortical actin to form a ramified transportation network beneath the immunological synapse. T cell activation and especially trafficking of T cell receptor microclusters during immunological synapse formation are widely thought to rely on cytoskeletal remodeling. However, important details on the involvement of actin in the latter transport processes are missing. Using a suite of advanced optical microscopes to analyze resting and activated T cells, we show that, following contact formation with activating surfaces, these cells sequentially rearrange their cortical actin across the entire cell, creating a previously unreported ramifying actin network above the immunological synapse. This network shows all the characteristics of an inward-growing transportation network and its dynamics correlating with T cell receptor rearrangements. This actin reorganization is accompanied by an increase in the nanoscale actin meshwork size and the dynamic adjustment of the turnover times and filament lengths of two differently sized filamentous actin populations, wherein formin-mediated long actin filaments support a very flat and stiff contact at the immunological synapse interface. The initiation of immunological synapse formation, as highlighted by calcium release, requires markedly little contact with activating surfaces and no cytoskeletal rearrangements. Our work suggests that incipient signaling in T cells initiates global cytoskeletal rearrangements across the whole cell, including a stiffening process for possibly mechanically supporting contact formation at the immunological synapse interface as well as a central ramified transportation network apparently directed at the consolidation of the contact and the delivery of effector functions.