Dynein self-organizes while translocating the centrosome in T-cells.
Dynein self-organizes while translocating the centrosome in T-cells.
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DOI：
10.1091/mbc.e20-10-0668
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发表时间：
2021-04-19
影响因子：
3.3
通讯作者：
Berger F
中科院分区：
文献类型：
--
作者：
Gros OJ;Damstra HGJ;Kapitein LC;Akhmanova A;Berger F
T细胞在到达抗原呈递细胞（APC）后大规模重构其内部结构以形成免疫突触（IS），免疫突触是有效消除APC所必需的细胞-细胞界面。这种重组通过细胞骨架过程的紧密协调发生：肌动蛋白形成外周环，动力蛋白马达将中心体向IS移位。最近的一项研究提出，中心体易位涉及一个微管（MT）束，它将中心体垂直连接到突触中心的动力蛋白：“柄”。然而，突触中心的肌动蛋白被耗尽，而肌动蛋白被认为是锚动力蛋白。我们提出动力蛋白附着在移动的膜锚上，并用计算机模拟研究了这个模型。我们发现，动力蛋白组织成一个集群的突触时，易位的中心体，对齐成柄MT。通过实现MT捕获收缩和MT滑动机制，我们明确表明，这种组织发生在这两个系统。然而，MT-滑动动力蛋白获得的结果更强大，并显示与我们的实验数据与膨胀显微镜一致的茎形态。因此，我们的模拟表明，肌动蛋白组织在T细胞激活过程中定义了一个特定的几何形状，其中MT滑动动力蛋白可以自组织成一个集群，并导致茎形成。
T-cells massively restructure their internal architecture upon reaching an antigen-presenting cell (APC) to form the immunological synapse (IS), a cell–cell interface necessary for efficient elimination of the APC. This reorganization occurs through tight coordination of cytoskeletal processes: actin forms a peripheral ring, and dynein motors translocate the centrosome toward the IS. A recent study proposed that centrosome translocation involves a microtubule (MT) bundle that connects the centrosome perpendicularly to dynein at the synapse center: the “stalk.” The synapse center, however, is actin-depleted, while actin was assumed to anchor dynein. We propose that dynein is attached to mobile membrane anchors, and investigate this model with computer simulations. We find that dynein organizes into a cluster in the synapse when translocating the centrosome, aligning MTs into a stalk. By implementing both a MT-capture-shrinkage and a MT-sliding mechanism, we explicitly demonstrate that this organization occurs in both systems. However, results obtained with MT-sliding dynein are more robust and display a stalk morphology consistent with our experimental data obtained with expansion microscopy. Thus, our simulations suggest that actin organization in T-cells during activation defines a specific geometry in which MT-sliding dynein can self-organize into a cluster and cause stalk formation.